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  • 1.
    Ali Khan, Ghazanfar
    et al.
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maqbool Khan, Kashif
    College of Pharmacy, University of Punjab, Lahore, Pakistan.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fick, Jerker
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Occurrence and Abundance of Antibiotics and Resistance Genes in Rivers, Canal and near Drug Formulation Facilities – A Study in Pakistan2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 6Article in journal (Refereed)
    Abstract [en]

    Antibiotic resistance (AR) is a global phenomenon that has severe epidemiological ramifications world-wide. It has been suggested that antibiotics that have been discharged into the natural aquatic environments after usage or manufacture can promote the occurrence of antibiotic resistance genes (ARG). These environmental ARGs could serve as a reservoir and be horizontally transferred to human-associated bacteria and thus contribute to AR proliferation. The aim of this study was to investigate the anthropogenic load of antibiotics in Northern Pakistan and study the occurrence of ARGs in selected samples from this region. 19 sampling sites were selected; including six rivers, one dam, one canal, one sewage drain and four drug formulation facilities. Our results show that five of the rivers have antibiotic levels comparable to surface water measurements in unpolluted sites in Europe and the US. However, high levels of antibiotics could be detected in the downstream river in close vicinity of the 10 million city Lahore, 1100, 1700 and 2700 ng L−1 for oxytetracycline, trimethoprim, and sulfamethoxazole respectively. Highest detected levels were at one of the drug formulation facilities, with the measured levels of 1100, 4100, 6200, 7300, 8000, 27000, 28000 and 49000 ng L−1 of erythromycin, lincomycin, ciprofloxacin, ofloxacin, levofloxacin, oxytetracycline, trimethoprim and sulfamethoxazole respectively. ARGs were also detected at the sites and the highest levels of ARGs detected, sulI and dfrA1, were directly associated with the antibiotics detected at the highest concentrations, sulfamethoxazole and trimethoprim. Highest levels of both antibiotics and ARGs were seen at a drug formulation facility, within an industrial estate with a low number of local residents and no hospitals in the vicinity, which indicates that the levels of ARGs at this site were associated with the environmental levels of antibiotics.

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  • 2. Order onlineBuy this publication >>
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Deliberations on the impact of antibiotic contamination on dissemination of antibiotic resistance genes in aquatic environments2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The great success of antibiotics in treating bacterial infectious diseases has been hampered by the increasing prevalence of antibiotic resistant bacteria. Not only does antibiotic resistance threaten to increase the difficulty in treating bacterial infectious diseases, but it could also make medical procedures such as routine surgery and organ transplantations very dangerous to perform. Traditionally, antibiotic resistance has been regarded as a strictly clinical problem and studies of the problem have mostly been restricted to a clinical milieu. Recently, non-clinical environments, and in particular aquatic environments, have been recognised as important factors in development and dissemination of antibiotic resistance. Elevated concentrations of antibiotics in an environment are likely to drive a selection pressure which favours resistant bacteria, and are also believed to promote horizontal gene transfer among the indigenous bacteria. Antibiotic resistance genes are often located on mobile genetic elements such as plasmids and integrons, which have the ability to disseminate among taxonomically unrelated species. The environmental bacteria can thus serve as both reservoirs for resistance and hot spots for the development of new antibiotic resistance determinants.

    There is still a lack of data pertaining to how high antibiotic concentrations are necessary to drive a selection pressure in aquatic environments. The aim of this thesis is to determine the effect of high and low concentrations of antibiotics on environmental bacterial  communities from different aquatic environments. In the studies performed, antibiotics were measured using liquid chromatography-mass spectrometry. Bacterial diversity and evenness were assessed using molecular fingerprints obtained with 16S rRNA gene-based denaturing gradient gel electrophoresis, and antibiotic resistance genes and class 1 integrons were quantified using real-time PCR.

    Water and sediment samples were collected from different rivers and canals in Pakistan. The environments differed in anthropogenic exposure from undisturbed to heavily contaminated. A general trend could be observed of high concentrations of antibiotics correlating to elevated concentrations of antibiotic resistance genes and integrons. Extremely high concentrations of antibiotic resistance genes and integrons were found in the sediments downstream of an industrial drug formulation site, which likely correlated to the high load of antibiotics found in the water. Antibiotic and antibiotic resistance gene concentrations were also shown to increase downstream of Ravi river, which flows through Lahore, a city of more than 10 million inhabitants. Rivers not impacted by anthropogenic contamination were found to contain antibiotics and resistance gene concentrations of similar levels as in Europe and the U.S. Similar measurements were performed in the Swedish river Stångån. The concentrations of antibiotic resistance genes and class 1 integrons were shown to increase in the river after it had passed, and received urban wastewater effluent from the city of Linköping.

    A series of constructed wetlands were exposed to a mixture of different antibiotics at environmentally relevant concentrations over a few weeks. The antibiotic exposure did not observably affect the bacterial diversity or integron concentrations. Antibiotic resistance genes were found at low background concentrations, but the antibiotic exposure did not observably affect the concentrations. The constructed wetlands were also found to reduce most antibiotics at levels comparable to conventional wastewater treatment schemes, suggesting that constructed wetlands may be useful supplementary alternatives to conventional wastewater treatment.

    To investigate the effect of antibiotics on an uncontaminated aquatic environment in a more controlled setting, microcosms were constructed from lake water and sediments and subsequently exposed to varying concentrations of antibiotics (ranging from wastewater-like concentrations to 1,000 times higher). The water and sediments were gathered from the lake Nydalasjön, near Umeå, which is not exposed to urban waste. While antibiotic resistance genes and class 1 integrons were found in the lake sediments, no increase in the concentrations of these genes could be observed due to the antibiotic additions.

    In conclusion, although antibiotic resistance genes and integrons are part of the environmental gene pool, low concentrations of antibiotics do not seem to immediately impact their prevalence. However, aquatic environments exposed to anthropogenic waste do exhibit elevated levels of antibiotic resistance genes and integrons. Aquatic environments heavily polluted with antibiotics also clearly display correspondingly high concentrations of antibiotic resistance genes and integrons. These results clearly indicate the necessity to keep down pollution levels as well as the need to establish the range of antibiotic concentrations which do promote resistance. This must be done in order to enable risk assessments and to establish acceptable levels of antibiotic pollution. It should also be stressed that more research is required to elucidate what effect low levels of antibiotic exposure has on environmental bacterial communities.

    List of papers
    1. Occurrence and Abundance of Antibiotics and Resistance Genes in Rivers, Canal and near Drug Formulation Facilities – A Study in Pakistan
    Open this publication in new window or tab >>Occurrence and Abundance of Antibiotics and Resistance Genes in Rivers, Canal and near Drug Formulation Facilities – A Study in Pakistan
    Show others...
    2013 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 6Article in journal (Refereed) Published
    Abstract [en]

    Antibiotic resistance (AR) is a global phenomenon that has severe epidemiological ramifications world-wide. It has been suggested that antibiotics that have been discharged into the natural aquatic environments after usage or manufacture can promote the occurrence of antibiotic resistance genes (ARG). These environmental ARGs could serve as a reservoir and be horizontally transferred to human-associated bacteria and thus contribute to AR proliferation. The aim of this study was to investigate the anthropogenic load of antibiotics in Northern Pakistan and study the occurrence of ARGs in selected samples from this region. 19 sampling sites were selected; including six rivers, one dam, one canal, one sewage drain and four drug formulation facilities. Our results show that five of the rivers have antibiotic levels comparable to surface water measurements in unpolluted sites in Europe and the US. However, high levels of antibiotics could be detected in the downstream river in close vicinity of the 10 million city Lahore, 1100, 1700 and 2700 ng L−1 for oxytetracycline, trimethoprim, and sulfamethoxazole respectively. Highest detected levels were at one of the drug formulation facilities, with the measured levels of 1100, 4100, 6200, 7300, 8000, 27000, 28000 and 49000 ng L−1 of erythromycin, lincomycin, ciprofloxacin, ofloxacin, levofloxacin, oxytetracycline, trimethoprim and sulfamethoxazole respectively. ARGs were also detected at the sites and the highest levels of ARGs detected, sulI and dfrA1, were directly associated with the antibiotics detected at the highest concentrations, sulfamethoxazole and trimethoprim. Highest levels of both antibiotics and ARGs were seen at a drug formulation facility, within an industrial estate with a low number of local residents and no hospitals in the vicinity, which indicates that the levels of ARGs at this site were associated with the environmental levels of antibiotics.

    Place, publisher, year, edition, pages
    Public Library of Science, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-96426 (URN)10.1371/journal.pone.0062712 (DOI)000321148400001 ()
    Note

    Funding Agencies|Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning FORMAS|210-2006-2132|Foundation for Strategic Environmental Research (MISTRA)||

    Available from: 2013-08-20 Created: 2013-08-19 Last updated: 2021-06-14
    2. Detection and Quantification of Antibiotic Resistance Genes in Stångån River, Sweden
    Open this publication in new window or tab >>Detection and Quantification of Antibiotic Resistance Genes in Stångån River, Sweden
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Antibiotic resistant bacteria are an emerging global problem which threatens to undermine important advances in modern medicine. It is becoming increasingly clear that the dynamics of antibiotic resistance are not confined to clinical settings. The environment is likely to play an important role in dissemination of antibiotic resistance genes from and to both environmental and pathogenic bacteria. Wastewater treatment plants accumulate both chemical and biological waste from the surrounding urban milieu and have therefore been viewed as potential hotspots for dissemination and development of antibiotic resistance. To assess the effect of wastewater effluent on a river which flows through a Swedish city, sediment and water samples were collected from Stångån River, both upstream and downstream of an adjacent wastewater treatment plant over three months. Seven antibiotic resistance genes and the integrase gene on class 1 integrons were quantified in the collected sediment using realtime PCR. Furthermore, liquid chromatography-mass spectrometry was used to assess the abundance of ten different antibiotics in the water phase of the samples. The results showed an increase in ARGs and integrons downstream of the wastewater treatment plant as compared to upstream. The measured concentrations of antibiotics were low in the water samples from Stångån River, suggesting that selection for antibiotic resistance genes did not occur in the surface water. Instead, the downstream increase in antibiotic resistance genes is likely to be due to accumulation of genes present in the treated effluent discharged from the wastewater treatment plant.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-105869 (URN)
    Available from: 2014-04-11 Created: 2014-04-11 Last updated: 2014-04-11
    3. Efficient removal of antibiotics in surface-flow constructed wetlands, with no observed impact on antibiotic resistance genes.
    Open this publication in new window or tab >>Efficient removal of antibiotics in surface-flow constructed wetlands, with no observed impact on antibiotic resistance genes.
    Show others...
    2014 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 476-477, p. 29-37Article in journal (Refereed) Published
    Abstract [en]

    Recently, there have been growing concerns about pharmaceuticals including antibiotics as environmental contaminants. Antibiotics of concentrations commonly encountered in wastewater have been suggested to affect bacterial population dynamics and to promote dissemination of antibiotic resistance. Conventional wastewater treatment processes do not always adequately remove pharmaceuticals causing environmental dissemination of low levels of these compounds. Using constructed wetlands as an additional treatment step after sewage treatment plants have been proposed as a cheap alternative to increase reduction of wastewater contaminants, however this means that the natural microbial community of the wetlands becomes exposed to elevated levels of antibiotics. In this study, experimental surface-flow wetlands in Sweden were continuously exposed to antibiotics of concentrations commonly encountered in wastewater. The aim was to assess the antibiotic removal efficiency of constructed wetlands and to evaluate the impact of low levels of antibiotics on bacterial diversity, resistance development and expression in the wetland bacterial community. Antibiotic concentrations were measured using liquid chromatography-mass spectrometry and the effect on the bacterial diversity was assessed with 16S rRNA-based denaturing gradient gel electrophoresis. Real-time PCR was used to detect and quantify antibiotic resistance genes and integrons in the wetlands, during and after the exposure period. The results indicated that the antibiotic removal efficiency of constructed wetlands was comparable to conventional wastewater treatment schemes. Furthermore, short-term treatment of the constructed wetlands with environmentally relevant concentrations (i.e. 100-2000 ng×l(-1)) of antibiotics did not significantly affect resistance gene concentrations, suggesting that surface-flow constructed wetlands are well-suited for wastewater treatment purposes.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Antibiotic resistance genes; Antibiotics; Quantitative real-time PCR; Constructed wetlands
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-105870 (URN)10.1016/j.scitotenv.2013.12.128 (DOI)000333772500004 ()24448029 (PubMedID)
    Available from: 2014-04-11 Created: 2014-04-11 Last updated: 2017-12-05Bibliographically approved
    4. Abundance and dynamics of antibiotic resistance genes and integrons in lake sediment microcosms
    Open this publication in new window or tab >>Abundance and dynamics of antibiotic resistance genes and integrons in lake sediment microcosms
    Show others...
    2014 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 9, p. e108151-Article in journal (Refereed) Published
    Abstract [en]

    Antibiotic resistance in bacteria causing disease is an ever growing threat to the world. Recently, environmental bacteria have become established as important both as sources of antibiotic resistance genes and in disseminating resistance genes. Low levels of antibiotics and other pharmaceuticals are regularly released into water environments via wastewater, and the concern is that such environmental contamination may serve to create hotspots for antibiotic resistance gene selection and dissemination. In this study, microcosms were created from water and sediments gathered from a lake in Sweden only lightly affected by human activities. The microcosms were exposed to a mixture of antibiotics of varying environmentally relevant concentrations (i.e., concentrations commonly encountered in wastewaters) in order to investigate the effect of low levels of antibiotics on antibiotic resistance gene abundances and dynamics in a previously uncontaminated environment. Antibiotic concentrations were measured using liquid chromatography-tandem mass spectrometry. Abundances of seven antibiotic resistance genes and the class 1 integron integrase gene, intL1, were quantified using real-time PCR. Resistance genes sulI and ermB were quantified in the microcosm sediments with mean abundances 5 and 15 gene copies/10(6) 16S rRNA gene copies, respectively. Class 1 integrons were determined in the sediments with a mean concentration of 3.86x10(4) copies/10(6) 16S rRNA gene copies. The antibiotic treatment had no observable effect on antibiotic resistance gene or integron abundances.

    National Category
    Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-105871 (URN)10.1371/journal.pone.0108151 (DOI)000342351800068 ()25247418 (PubMedID)
    Available from: 2014-04-11 Created: 2014-04-11 Last updated: 2021-06-14Bibliographically approved
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    Deliberations on the impact of antibiotic contamination on dissemination of antibiotic resistance genes in aquatic environments
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  • 3.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Bich Hoang, Ngoc Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kien Le, Ngai
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Khanh Khu, Dung Thi
    Vietnam Natl Childrens Hosp, Vietnam; TRAC Sweden Vietnam, Vietnam.
    Svartström, Olov
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Olson, Linus
    TRAC Sweden Vietnam, Vietnam; Karolinska Inst, Sweden.
    Minh Dien, Tran
    Vietnam Natl Childrens Hosp, Vietnam.
    Thanh Le, Hai
    Vietnam Natl Childrens Hosp, Vietnam; TRAC Sweden Vietnam, Vietnam.
    Larsson, Mattias
    TRAC Sweden Vietnam, Vietnam; Karolinska Inst, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. TRAC Sweden Vietnam, Vietnam.
    Molecular and phenotypic characterization of clinical isolates belonging to a KPC-2-producing strain of ST15 Klebsiella pneumoniae from a Vietnamese pediatric hospital2019In: Antimicrobial Resistance and Infection Control, E-ISSN 2047-2994, Vol. 8, no 1, article id 156Article in journal (Refereed)
    Abstract [en]

    Background Carbapenem-resistant Klebsiella pneumoniae are becoming increasingly common in hospital settings worldwide and are a source of increased morbidity, mortality and health care costs. The global epidemiology of carbapenem-resistant K. pneumoniae is characterized by different strains distributed geographically, with the strain ST258 being predominant in Europe and USA, and ST11 being most common in East Asia. ST15 is a less frequently occurring strain but has nevertheless been reported worldwide as a source of hospital outbreaks of carbapenem-resistant K. pneumoniae. Methods In this study, whole-genome sequencing and antimicrobial susceptibility testing was used to characterize 57 clinical isolates of carbapenem-resistant K. pneumoniae belonging to a strain of ST15, which were collected at a Vietnamese pediatric hospital from February throughout September 2015. Results Aside from the carbapenem resistance gene bla(KPC-2), which was carried by all isolates, prevalence of resistance genes to other antibiotics including aminoglycosides, macrolides, quinolones, fosfomycin and trimethoprim, was also high. All isolates were multidrug-resistant. Susceptibility was highest to ceftazidime/avibactam (96%), gentamicin (91%) and tigecycline (82%). Notably, the colistin resistance rate was very high (42%). Single-nucleotide polymorphism analysis indicated that most isolates belonged to a single clone. Conclusions The diverse variety of antibiotic resistance genes and the high antibiotic resistance rates to last-resort antibiotics such as carbapenems and colistin, is indicative of a highly adaptable strain. This emphasizes the importance of implementation of infection controls measures, continued monitoring of antibiotic resistance and prudent use of antibiotics to prevent further selection of resistant strains and the emergence of pan-resistant clones.

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  • 4.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bich Hoang, Ngoc Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kien Le, Ngai
    Vietnam Natl Childrens Hosp, Vietnam.
    Svartström, Olov
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Khanh Khu, Dung Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Thanh Le, Hai
    Vietnam Natl Childrens Hosp, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Olson, Linus
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Larsson, Mattias
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. TRAC, Sweden; TRAC, Vietnam.
    Insertion sequence transpositions and point mutations in mgrB causing colistin resistance in a clinical strain of carbapenem-resistant Klebsiella pneumoniae from Vietnam2018In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 51, no 5, p. 789-793Article in journal (Refereed)
    Abstract [en]

    Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems and colistin is increasing worldwide. In this study, whole-genome sequencing was used to determine the colistin resistance mechanisms in clinical isolates of carbapenem-and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, were found in 30 of 31 isolates, emphasising the importance of this resistance mechanism in colistin-resistant K. pneumoniae. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  • 5.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Chen, Baoli
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Qiang
    Shandong Univ, Peoples R China.
    Xu, Liuchen
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Li, Yan
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Bi, Zhenwang
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Characterization of extended-spectrum -lactamase-producing Escherichia coli harboring mcr-1 and toxin genes from human fecal samples from China2018In: Future Microbiology, ISSN 1746-0913, E-ISSN 1746-0921, Vol. 13, no 15, p. 1647-1656Article in journal (Refereed)
    Abstract [en]

    Aim: To characterize extended-spectrum -lactamase-producing Escherichia coli harboring the colistin resistance gene mcr-1 from human fecal samples collected in 2012 in a rural area of Shandong province, PR China. Materials amp; methods: Whole-genome sequencing and antimicrobial susceptibility testing was performed on 25 mcr-1-positive isolates to determine carriage of antibiotic resistance and virulence genes, diversity and antibiotic resistance profiles. Results: The isolates were highly genetically diverse and carried a large variety of different antibiotic resistance genes. The multidrug-resistance rate was high (96%). Virulence genes associated with intestinal pathogenic E. coli were carried by 32% of the isolates. Conclusion: Further monitoring of the epidemiological situation is necessary to ensure a preparedness for potential emergence of novel, difficult-to-treat strains and awareness of available treatment options.

  • 6.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Letter: High Prevalence of Heterogeneously Glycopeptide-Intermediate Coagulase-Negative Staphylococci in Sternal Wounds in ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol 60, issue 8, pp 5097-50982016In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 8, p. 5097-5098Article in journal (Other academic)
    Abstract [en]

    n/a

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    fulltext
  • 7.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dienus, Olaf
    County Hospital Ryhov, Sweden.
    Sokolova, Ekaterina
    Chalmers, Sweden.
    Berglind, Emma
    County Hospital Ryhov, Sweden.
    Matussek, Andreas
    County Hospital Ryhov, Sweden; Karolinska University of Lab, Sweden.
    Pettersson, Thomas
    Chalmers, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Occurrence and removal efficiency of parasitic protozoa in Swedish wastewater treatment plants2017In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 598, p. 821-827Article in journal (Refereed)
    Abstract [en]

    Giardia intestinalis, Cryptosporidium spp., Entamoeba histolytica and Dientamoeba fragilis are parasitic protozoa and causative agents of gastroenteritis in humans. G. intestinalis and Cryptosporidium spp. in particular are the most common protozoa associated with waterborne outbreaks in high-income countries. Surveillance of protozoan prevalence in wastewater and evaluation of wastewater treatment removal efficiencies of protozoan pathogens is therefore imperative for assessment of human health risk. In this study, influent and effluent wastewater samples from three wastewater treatment plants in Sweden were collected over nearly one year and assessed for prevalence of parasitic protozoa. Quantitative real-time PCR using primers specific for the selected protozoa Cryptosporidium spp., G, intestinalis, E. histolytica, Entamoeba dispar and D. fragilis was used for protozoan DNA detection and assessment of wastewater treatment removal efficiencies. Occurrence of G. intestinalis, E. dispar and D. fragilis DNA was assessed in both influent (44, 30 and 39 out of 51 samples respectively) and effluent wastewater (14, 9 and 33 out of 51 samples respectively) in all three wastewater treatment plants. Mean removal efficiencies of G. intestinalis, E. dispar and D. fragilis DNA quantities, based on all three wastewater treatment plants studied varied between 67 and 87%, 37-75% and 20-34% respectively. Neither E. histolytica nor Cryptosporidium spp. were detected in any samples. Overall, higher quantities of protozoan DNA were observed from February to June 2012. The high prevalence of protozoa in influent wastewater indicates the need for continued monitoring of these pathogens in wastewater-associated aquatic environments to minimise the potential risk for human infection. (C) 2017 Elsevier B.V. All rights reserved.

  • 8.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fick, Jerker
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Department of Microbiology, Medical Services, County Hospital Ryhov, Jönköping, Sweden.
    Detection and Quantification of Antibiotic Resistance Genes in Stångån River, Sweden2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Antibiotic resistant bacteria are an emerging global problem which threatens to undermine important advances in modern medicine. It is becoming increasingly clear that the dynamics of antibiotic resistance are not confined to clinical settings. The environment is likely to play an important role in dissemination of antibiotic resistance genes from and to both environmental and pathogenic bacteria. Wastewater treatment plants accumulate both chemical and biological waste from the surrounding urban milieu and have therefore been viewed as potential hotspots for dissemination and development of antibiotic resistance. To assess the effect of wastewater effluent on a river which flows through a Swedish city, sediment and water samples were collected from Stångån River, both upstream and downstream of an adjacent wastewater treatment plant over three months. Seven antibiotic resistance genes and the integrase gene on class 1 integrons were quantified in the collected sediment using realtime PCR. Furthermore, liquid chromatography-mass spectrometry was used to assess the abundance of ten different antibiotics in the water phase of the samples. The results showed an increase in ARGs and integrons downstream of the wastewater treatment plant as compared to upstream. The measured concentrations of antibiotics were low in the water samples from Stångån River, suggesting that selection for antibiotic resistance genes did not occur in the surface water. Instead, the downstream increase in antibiotic resistance genes is likely to be due to accumulation of genes present in the treated effluent discharged from the wastewater treatment plant.

  • 9.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fick, Jerker
    Umeå University, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. County Hospital Ryhov, Sweden.
    URBAN WASTEWATER EFFLUENT INCREASES ANTIBIOTIC RESISTANCE GENE CONCENTRATIONS IN A RECEIVING NORTHERN EUROPEAN RIVER2015In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 34, no 1, p. 192-196Article in journal (Refereed)
    Abstract [en]

    Antibiotic-resistant bacteria are an emerging global problem that threatens to undermine important advances in modern medicine. The environment is likely to play an important role in the dissemination of antibiotic-resistance genes (ARGs) among both environmental and pathogenic bacteria. Wastewater treatment plants (WWTPs) accumulate both chemical and biological waste from the surrounding urban milieu and have therefore been viewed as potential hotspots for dissemination and development of antibiotic resistance. To assess the effect of wastewater effluent on a river that flows through a Swedish city, sediment and water samples were collected from Stangan River, both upstream and downstream of an adjacent WWTP over 3 mo. Seven ARGs and the integrase gene on class 1 integrons were quantified in the collected sediment using real-time polymerase chain reaction (PCR). Liquid chromatography-mass spectrometry was used to assess the abundance of 10 different antibiotics in the water phase of the samples. The results showed an increase in ARGs and integrons downstream of the WWTP. The measured concentrations of antibiotics were low in the water samples from the Stangan River, suggesting that selection for ARGs did not occur in the surface water. Instead, the downstream increase in ARGs is likely to be attributable to accumulation of genes present in the treated effluent discharged from the WWTP. Environ Toxicol Chem 2015;34:192-196. (c) 2014 SETAC

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  • 10.
    Berglund, Björn
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Hoang, Ngoc Thi Bich
    Vietnam Natl Childrens Hosp, Vietnam.
    Lundberg, Ludwig
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Swedish Univ Agr Sci, Sweden.
    Le, Ngai Kien
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Services and Infrastructure. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Bornefall, Elin
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Khu, Dung Thi Khanh
    Vietnam Natl Childrens Hosp, Vietnam; Training & Res Acad Collaborat TRAC Sweden Vietna, Vietnam.
    Welander, Jenny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Le, Hai Thanh
    Vietnam Natl Childrens Hosp, Vietnam; Training & Res Acad Collaborat TRAC Sweden Vietna, Vietnam.
    Olson, Linus
    Training & Res Acad Collaborat TRAC Sweden Vietna, Vietnam; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Dien, Tran Minh
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Lennart E
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Mattias
    Training & Res Acad Collaborat TRAC Sweden Vietna, Vietnam; Karolinska Inst, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases. Training & Res Acad Collaborat TRAC Sweden Vietna, Vietnam.
    Clonal spread of carbapenem-resistant Klebsiella pneumoniae among patients at admission and discharge at a Vietnamese neonatal intensive care unit2021In: Antimicrobial Resistance and Infection Control, E-ISSN 2047-2994, Vol. 10, no 1, article id 162Article in journal (Refereed)
    Abstract [en]

    Background The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is a growing problem globally, particularly in low- to middle-income countries (LMICs). Previous studies have shown high rates of CRE colonisation among patients at hospitals in LMICs, with increased risk of hospital-acquired infections. Methods We isolated carbapenem-resistant Klebsiella pneumoniae (CRKP) from faecal samples collected in 2017 from patients at admission and discharge at a Vietnamese neonatal intensive care unit (NICU). 126 CRKP were whole-genome sequenced. The phylogenetic relationship between the isolates and between clinical CRKP isolates collected in 2012-2018 at the same hospital were investigated. Results NDM-type carbapenemase-(61%) and KPC-2-encoding genes (41%) were the most common carbapenem resistance genes observed among the admission and discharge isolates. Most isolates (56%) belonged to three distinct clonal clusters of ST15, carrying bla(KPC-2), bla(NDM-1) and bla(NDM-4), respectively. Each cluster also comprised clinical isolates from blood collected at the study hospital. The most dominant ST15 clone was shown to be related to isolates collected from the same hospital as far back as in 2012. Conclusions Highly resistant CRKP were found colonising admission and discharge patients at a Vietnamese NICU, emphasising the importance of continued monitoring. Whole-genome sequencing revealed a population of CRKP consisting mostly of ST15 isolates in three clonally related clusters, each related to blood isolates collected from the same hospital. Furthermore, clinical isolates collected from previous years (dating back to 2012) were shown to likely be clonally descended from ST15 isolates in the largest cluster, suggesting a successful hospital strain which can colonise inpatients.

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  • 11.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hoang, Ngoc Thi Bich
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Le, Ngai Kien
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Khu, Dung Thi Khanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Olson, Linus
    The Karolinska Institute, Stockholm, Sweden.
    Le, Hai Thanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Larsson, Mattias
    The Karolinska Institute, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Colistin- and carbapenem-resistant Klebsiella pneumoniae carrying mcr-1 and bla(OXA-48) isolated at a paediatric hospital in Vietnam2018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 4, p. 1100-1102Article in journal (Other academic)
    Abstract [en]

    n/a

  • 12.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Khan, Ghazanfar Ali
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Lindberg, Richard
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Fick, Jerker
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Abundance and dynamics of antibiotic resistance genes and integrons in lake sediment microcosms2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 9, p. e108151-Article in journal (Refereed)
    Abstract [en]

    Antibiotic resistance in bacteria causing disease is an ever growing threat to the world. Recently, environmental bacteria have become established as important both as sources of antibiotic resistance genes and in disseminating resistance genes. Low levels of antibiotics and other pharmaceuticals are regularly released into water environments via wastewater, and the concern is that such environmental contamination may serve to create hotspots for antibiotic resistance gene selection and dissemination. In this study, microcosms were created from water and sediments gathered from a lake in Sweden only lightly affected by human activities. The microcosms were exposed to a mixture of antibiotics of varying environmentally relevant concentrations (i.e., concentrations commonly encountered in wastewaters) in order to investigate the effect of low levels of antibiotics on antibiotic resistance gene abundances and dynamics in a previously uncontaminated environment. Antibiotic concentrations were measured using liquid chromatography-tandem mass spectrometry. Abundances of seven antibiotic resistance genes and the class 1 integron integrase gene, intL1, were quantified using real-time PCR. Resistance genes sulI and ermB were quantified in the microcosm sediments with mean abundances 5 and 15 gene copies/10(6) 16S rRNA gene copies, respectively. Class 1 integrons were determined in the sediments with a mean concentration of 3.86x10(4) copies/10(6) 16S rRNA gene copies. The antibiotic treatment had no observable effect on antibiotic resistance gene or integron abundances.

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  • 13.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Khan, Ghazanfar Ali
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Weisner, Stefan E B
    Wetland Research Centre, Halmstad University, Halmstad, Sweden.
    Ehde, Per Magnus
    Wetland Research Centre, Halmstad University, Halmstad, Sweden.
    Fick, Jerker
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Efficient removal of antibiotics in surface-flow constructed wetlands, with no observed impact on antibiotic resistance genes.2014In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 476-477, p. 29-37Article in journal (Refereed)
    Abstract [en]

    Recently, there have been growing concerns about pharmaceuticals including antibiotics as environmental contaminants. Antibiotics of concentrations commonly encountered in wastewater have been suggested to affect bacterial population dynamics and to promote dissemination of antibiotic resistance. Conventional wastewater treatment processes do not always adequately remove pharmaceuticals causing environmental dissemination of low levels of these compounds. Using constructed wetlands as an additional treatment step after sewage treatment plants have been proposed as a cheap alternative to increase reduction of wastewater contaminants, however this means that the natural microbial community of the wetlands becomes exposed to elevated levels of antibiotics. In this study, experimental surface-flow wetlands in Sweden were continuously exposed to antibiotics of concentrations commonly encountered in wastewater. The aim was to assess the antibiotic removal efficiency of constructed wetlands and to evaluate the impact of low levels of antibiotics on bacterial diversity, resistance development and expression in the wetland bacterial community. Antibiotic concentrations were measured using liquid chromatography-mass spectrometry and the effect on the bacterial diversity was assessed with 16S rRNA-based denaturing gradient gel electrophoresis. Real-time PCR was used to detect and quantify antibiotic resistance genes and integrons in the wetlands, during and after the exposure period. The results indicated that the antibiotic removal efficiency of constructed wetlands was comparable to conventional wastewater treatment schemes. Furthermore, short-term treatment of the constructed wetlands with environmentally relevant concentrations (i.e. 100-2000 ng×l(-1)) of antibiotics did not significantly affect resistance gene concentrations, suggesting that surface-flow constructed wetlands are well-suited for wastewater treatment purposes.

  • 14.
    Bi, Z.
    et al.
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Sun, C.
    China Agr Univ, Peoples R China.
    Borjesson, S.
    Natl Vet Inst SVA, Sweden.
    Chen, B.
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Ji, X.
    China Agr Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wang, M.
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Yin, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Q.
    Shandong Univ, Peoples R China; Shandong Univ, Peoples R China.
    Hulth, A.
    Publ Hlth Agcy Sweden, Sweden.
    Wang, Y.
    China Agr Univ, Peoples R China.
    Wu, C.
    China Agr Univ, Peoples R China.
    Bi, Z.
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Identical genotypes of community-associated MRSA (ST59) and livestock-associated MRSA (ST9) in humans and pigs in rural China2018In: Zoonoses and Public Health, ISSN 1863-1959, E-ISSN 1863-2378, Vol. 65, no 3, p. 367-371Article in journal (Refereed)
    Abstract [en]

    This study investigated the prevalence of MRSA in samples taken in households, with and without backyard pigs in villages in a rural area of Shandong Province, China. Community-associated MRSA and livestock-associated MRSA, belonging to ST59 and ST9, respectively, were identified in both humans and pigs. The genotypic and phenotypic comparison of isolates indicates that bidirectional transmission of MRSA has occurred between humans and pigs in the villages.

  • 15.
    Bi, Zhenwang
    et al.
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Qiang
    Shandong University, Peoples R China; Shandong University, Peoples R China.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Chen, Baoli
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ding, Lilu
    Shandong University, Peoples R China.
    Stalsby Lundborg, Cecilia
    Karolinska Institute, Sweden.
    Bi, Zhenqiang
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Tomson, Goran
    Karolinska Institute, Sweden.
    Yao, Jingjing
    Shandong University, Peoples R China.
    Gu, Zhanying
    Shandong University, Peoples R China.
    Yin, Xiao
    Jinan Central Hospital, Peoples R China.
    Kou, Zengqiang
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Prevalence of the mcr-1 colistin resistance gene in extended-spectrum beta-lactamase-producing Escherichia coli from human faecal samples collected in 2012 in rural villages in Shandong Province, China2017In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 49, no 4, p. 493-497Article in journal (Refereed)
    Abstract [en]

    Since its initial discovery in China in 2015, the plasmid-mediated colistin resistance gene mcr-1 has been reported in Escherichia coli isolated from clinical samples, animals and meat worldwide. In this study, 706 extended-spectrum beta-lactamase (ESBL)-producing E. coli from 411 persons were detected in a collection of faecal samples from 1000 rural residents in three counties in Shandong Province, China. These isolates were screened for mcr-1 and phenotypic colistin resistance. The gene was found in 3.5% of the isolates (from 4.9% of persons) from all three counties. All isolates with phenotypic colistin resistance carried mcr-1. These data indicate that commensal carriage of ESBL-producing E. coli with mcr-1 among persons in rural China was already present in 2012 and that mcr-1 was the most important colistin resistance mechanism. Interventions are necessary to minimise further dissemination of mcr-1, which would limit the future usefulness of colistin as a last-resort antibiotic. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  • 16.
    Chi, Xiaohui
    et al.
    Shandong Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Zhejiang Univ, Peoples R China.
    Zou, Huiyun
    Shandong Univ, Peoples R China.
    Zheng, Beiwen
    Zhejiang Univ, Peoples R China.
    Börjesson, Stefan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Natl Vet Inst, Sweden.
    Ji, Xiang
    Shandong Univ, Peoples R China.
    Ottoson, Jakob
    Natl Food Agcy, Sweden.
    Lundborg, Cecilia Stalsby
    Karolinska Inst, Sweden.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Nilsson, Lennart E
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Characterization of Clinically Relevant Strains of Extended-Spectrum beta-Lactamase-Producing Klebsiella pneumoniae Occurring in Environmental Sources in a Rural Area of China by Using Whole-Genome Sequencing2019In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 10, article id 211Article in journal (Refereed)
    Abstract [en]

    Klebsiella pneumoniae is a gram-negative, opportunistic pathogen, and a common cause of healthcare-associated infections such as pneumonia, septicemia, and urinary tract infection. The purpose of this study was to survey the occurrence of and characterize K. pneumoniae in different environmental sources in a rural area of Shandong province, China. Two hundred and thirty-one samples from different environmental sources in 12 villages were screened for extended-spectrum beta-lactamase-(ESBL)-producing K. pneumoniae, and 14 (6%) samples were positive. All isolates were multidrug-resistant and a few of them belonged to clinically relevant strains which are known to cause hospital outbreaks worldwide. Serotypes, virulence genes, serum survival, and phagocytosis survival were analyzed and the results showed the presence of virulence factors associated with highly virulent clones and a high degree of phagocytosis survivability, indicating the potential virulence of these isolates. These results emphasize the need for further studies designed to elucidate the role of the environment in transmission and dissemination of ESBL-producing K. pneumoniae and the potential risk posed to human and environmental health.

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  • 17.
    Fei, Yiqiu
    et al.
    Zhejiang Univ, Peoples R China.
    Chen, Zuobing
    Zhejiang Univ, Peoples R China.
    Han, Shengyi
    Zhejiang Univ, Peoples R China.
    Zhang, Shuobo
    Zhejiang Univ, Peoples R China.
    Zhang, Tianfang
    Zhejiang Univ, Peoples R China.
    Lu, Yanmeng
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Xiao, Hang
    Univ Massachusetts, MA 01002 USA.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China.
    Yao, Mingfei
    Zhejiang Univ, Peoples R China.
    Role of prebiotics in enhancing the function of next-generation probiotics in gut microbiota2023In: Critical reviews in food science and nutrition, ISSN 1040-8398, E-ISSN 1549-7852, Vol. 63, no 8, p. 1037-1054Article, review/survey (Refereed)
    Abstract [en]

    With the development of high-throughput DNA sequencing and molecular analysis technologies, next-generation probiotics (NGPs) are increasingly gaining attention as live bacterial therapeutics for treatment of diseases. However, compared to traditional probiotics, NGPs are much more vulnerable to the harsh conditions in the human gastrointestinal tract, and their functional mechanisms in the gut are more complex. Prebiotics have been confirmed to play a critical role in improving the function and viability of traditional probiotics. Defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, prebiotics are also important for NGPs. This review summarizes potential prebiotics for use with NGPs and clarifies their characteristics and functional mechanisms. Then we particularly focus on illustrating the protective effects of various prebiotics by enhancing the antioxidant capacity and their resistance to digestive fluids. We also elucidate the role of prebiotics in regulating anti-bacterial effects, intestinal barrier maintenance, and cross-feeding mechanisms of NPGs. With the expanding range of candidate NGPs and prebiotic substrates, more studies need to be conducted to comprehensively elucidate the interactions between prebiotics and NGPs outside and inside hosts, in order to boost their nutritional and healthcare applications.

  • 18.
    Fei, Yiqiu
    et al.
    Zhejiang Univ, Peoples R China.
    Zhang, Shuobo
    Zhejiang Univ, Peoples R China.
    Han, Shengyi
    Zhejiang Univ, Peoples R China.
    Qiu, Bo
    Zhejiang Univ, Peoples R China.
    Lu, Yanmeng
    Zhejiang Univ, Peoples R China.
    Huang, Weixing
    Jinan Microecol Biomed Shandong Lab, Peoples R China; Zhejiang Tongchuang Yuecheng Hlth Sci & Technol, Peoples R China.
    Li, Fang
    Columbia Univ, NY 10032 USA; Univ Massachusetts, MA 01003 USA.
    Chen, Deying
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Xiao, Hang
    Univ Massachusetts, MA 01003 USA; Zhejiang Univ, Peoples R China.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China; Jinan Microecol Biomed Shandong Lab, Peoples R China.
    Yao, Mingfei
    Zhejiang Univ, Peoples R China.
    The Role of Dihydroresveratrol in Enhancing the Synergistic Effect of Ligilactobacillus salivarius Li01 and Resveratrol in Ameliorating Colitis in Mice2022In: Research, ISSN 2096-5168, Vol. 2022, article id 9863845Article in journal (Refereed)
    Abstract [en]

    Currently approved therapeutical strategies for inflammatory bowel diseases (IBD) suffer from variable efficacy and association with risk of serious side effects. Therefore, efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation. In this study, we show that the probiotic strain Ligilactobacillus salivarius Li01 (Li01) and the phytochemical prebiotic resveratrol (RSV) have synergistic effect in ameliorating colitis in mice. Oral coadministration of Li01 (10(9) CFU/d) and RSV (1.5 g/kg/d) promoted restoration of various inflammatory injuries and gut microbiota composition, exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice. The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1 beta and IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum. Moreover, the combination treatment was found to alter the composition and metabolism of the gut microbiota, especially influencing the production of short chain fatty acids and anti-inflammatory related molecules. The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor (AHR) and tryptophan metabolism pathway. Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites, including dihydroresveratrol (DHR), resveratrol-sulfate, and resveratrol-glucuronide. DHR was found to be the dominant metabolite of RSV in conventional and colitis mice. An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect. DHR is considered as a potential AHR ligand. The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1, SERT, and 5-HT7R leading to amelioration of colitis in mice. Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD; further investigation of this combination in clinical settings is warranted.

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  • 19.
    Gu, Congcong
    et al.
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Zou, Huiyun
    Shandong Univ, Peoples R China.
    Zhao, Ling
    Shandong Univ, Peoples R China.
    Meng, Chen
    Shandong Univ, Peoples R China.
    Yang, Chengxia
    Shandong Univ, Peoples R China.
    Zhang, Hui
    Shandong Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Clonal and plasmid-mediated dissemination of environmental carbapenem-resistant Enterobacteriaceae in large animal breeding areas in northern China2022In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 297, article id 118800Article in journal (Refereed)
    Abstract [en]

    The emergence and dissemination of carbapenem-resistant Enterobacteriaceae (CRE) constitute a major global health problem. The environment plays an important role in the dissemination of CRE, but large-scale studies on CRE in groundwater environments in animal breeding areas are scarce. The aim of this study was to investigate CRE occurrence and environmental transmission of carbapenem resistance genes in large animal breeding areas in northern China. In total, 280 well water and 102 animal feces samples in large animal breeding areas in six counties from the two provinces Inner Mongolia and Shandong in China, were screened for CRE. A total of 39 CRE were isolated and characterized with next-generation sequencing. 5.3% of well water samples were contaminated with CRE. The well water in chicken farms had the highest number of detections of CRE (15.9%). More than half of the isolates carried closely related, conjugative IncX3 plasmids with blaNDM-genes from multiple geographic areas, indicating that this kind of plasmid plays an important role in dissemination of carbapenem resistance determinants. The clonal expansion of various CRE isolates in well water and animal feces were demonstrated; clonally related CRE were isolated from different wells within the same county, from different counties in the same province, and even from different provinces. In addition to harboring various ARGs, two closely related K. pneumoniae belonging to ST11 isolated from well water carried genetic hypervirulence determinants on a virulence plasmid, highlighting the potential health risk posed by further dissemination of this strain. These findings suggest that groundwater may be an underappreciated reservoir and source of dissemination of CRE, from which resistance genes may disseminate among different bacterial strains and over large geographic distances. Further research and multi-sectorial monitoring, with a "One health" perspective, is urgently needed to investigate the need for interventions aimed at preventing CRE dissemination.

  • 20.
    Han, Shengyi
    et al.
    Zhejiang Univ, Peoples R China.
    Lu, Yanmeng
    Zhejiang Univ, Peoples R China.
    Xie, Jiaojiao
    Zhejiang Univ, Peoples R China.
    Fei, Yiqiu
    Zhejiang Univ, Peoples R China.
    Zheng, Guiwen
    Zhejiang Univ, Peoples R China.
    Wang, Ziyuan
    Beijing Technol & Business Univ BTBU, Peoples R China.
    Liu, Jie
    Beijing Technol & Business Univ BTBU, Peoples R China.
    Lv, Longxian
    Zhejiang Univ, Peoples R China.
    Ling, Zongxin
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Yao, Mingfei
    Zhejiang Univ, Peoples R China.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China.
    Probiotic Gastrointestinal Transit and Colonization After Oral Administration: A Long Journey2021In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 11, article id 609722Article, review/survey (Refereed)
    Abstract [en]

    Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization.

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  • 21.
    Hanna, Nada
    et al.
    Karolinska Inst, Sweden.
    Sun, Pan
    Shandong Univ, Peoples R China.
    Sun, Qiang
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Yang, Xiwei
    Shandong Univ, Peoples R China.
    Ji, Xiang
    Shandong Univ, Peoples R China.
    Zou, Huiyun
    Shandong Univ, Peoples R China.
    Ottoson, Jakob
    Natl Food Agcy, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dyar, Oliver James
    Karolinska Inst, Sweden.
    Tamhankar, Ashok J.
    Karolinska Inst, Sweden.
    Lundborg, Cecilia Stalsby
    Karolinska Inst, Sweden.
    Presence of antibiotic residues in various environmental compartments of Shandong province in eastern China: Its potential for resistance development and ecological and human risk2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 114, p. 131-142Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the occurrence of antibiotic residues in different types of environmental samples including water samples in rural Shandong province, China. Further, to characterize the potential ecological risk for development of antibiotic resistance in the environment, and the potential direct human health risk of exposure to antibiotics via drinking water and vegetables. Methods: Environmental samples (n = 214) (river water, waste water, drinking water, sediments, manure, soil and edible parts of vegetables) were collected in twelve villages in Shandong province in eastern China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to determine the concentration of antibiotic residues. The ratio of the measured environmental concentrations (MEC) to the predicted no-effect concentrations (PNEC) was used to evaluate the ecological risk (risk quotient, RQ) for development of antibiotic resistance. The potential risks to human health through exposure to antibiotics in drinking water were assessed by comparing measured environmental concentrations (MEC) and predicted no-effect concentration in drinking water (PNECDW), and in vegetables by comparing estimated daily intake (EDI) to ADI. Results: Sulfapyridine, sulfamethoxazole, ciprofloxacin, enrofloxacin, levofloxacin, norfloxacin, chloramphenicol, florfenicol, doxycycline, and metronidazole were detected at concentrations ranging between 0.3 and 3.9 ng/L in river water, 1.3 and 12.5 ng/L in waste water, 0.5 and 21.4 ng/L in drinking water, 0.31 and 1.21 mu g/kg in river sediment, 0.82 and 1.91 mu g/kg in pig manure, 0.1 and 11.68 mu g/kg in outlet sediment, 0.5 and 2.5 mu g/kg in soil, and 6.3 and 27.2 mu g/kg in vegetables. The RQs for resistance development were amp;gt; 1 for enrofloxacin, levofloxacin, and ranged between 0.1 and 1 for ciprofloxacin. MECs/PNECDW ratios were amp;lt; 1 from exposure to antibiotics through drinking water for both adults and children. EDI/ADI ratios were amp;lt; 0.1 from exposure to antibiotics by vegetable consumption. Conclusions: Antibiotic pollutants were ubiquitous in various environmental compartments of Shandong province of China. Risk estimates indicated a potential for the measured levels of enrofloxacin, levofloxacin and ciprofloxacin in waste water to pose an ecological risk for resistance selection, and further studies are needed to validate this finding. The investigated antibiotics did not appear to pose an appreciable direct human health risk from environmental exposure through drinking water or vegetables consumption. However, they might still pose a risk for resistance development.

  • 22.
    Holmbom, Martin
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection.
    Möller, Vidar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Kristinsdottir, Lóa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Maud
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Rashid, Mamun-Ur
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Östholm Balkhed, Åse
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Risk factors and outcome due to extended-spectrum beta-lactamase-producing uropathogenic Escherichia coli in community-onset bloodstream infections: A ten-year cohort study in Sweden2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 11, article id e0277054Article in journal (Refereed)
    Abstract [en]

    Objective To study clinical outcome and risk factors associated with extended-spectrum beta-lactamase (ESBL)-producing uropathogenic Escherichia coli (UPEC) in community-onset bloodstream infections (CO-BSI). Methods This was a population-based cohort study including patients with pheno- and genotype-matched ESBL-producing E. coli and non-ESBL- E. coli in urine and blood samples collected in 2009-2018 in southeast Sweden. Seventy-seven episodes of ESBL-UPEC satisfying the inclusion criteria were matched 1:1 with 77 non-ESBL-UPEC for age, gender, and year of culture. Results The most common ST-type and ESBL gene was ST131 (55%), and bla(CTX-M-15) (47%), respectively. Risk factors for ESBL-UPEC were: previous genitourinary invasive procedure (RR 4.66; p = 0.005) or history of ESBL-producing E. coli (RR 12.14; p = 0.024). There was significant difference between ESBL-UPEC and non-ESBL-UPEC regarding time to microbiologically appropriate antibiotic therapy (27:15 h vs. 02:14 h; p = <0.001) and hospital days (9 vs. 5; p = <0.001), but no difference in 30-day mortality (3% vs. 3%; p = >0.999) or sepsis within 36 hours (51% vs. 62%; p = 0.623) was observed. Conclusion The predominant risk factors for ESBL-UPEC were history of ESBL-Ec infection and history of genitourinary invasive procedure. The overall mortality was low and the delay in appropriate antibiotic therapy did not increase the risk for 30-day mortality or risk for sepsis within 36 hours among patients infected with ESBL UPEC. However, these results must be regarded with some degree of caution due to the small sample size.

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  • 23.
    Ji, Xiang
    et al.
    Shandong Univ, Peoples R China.
    Zheng, Beiwen
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Zou, Huiyun
    Shandong Univ, Peoples R China.
    Sun, Qiang
    Shandong Univ, Peoples R China.
    Chi, Xiaohui
    Shandong Univ, Peoples R China.
    Ottoson, Jakob
    Natl Food Agcy, Sweden.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Lundborg, Cecilia Stalsby
    Karolinska Inst, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Dissemination of extended-spectrum beta-lactamase-producing Escherichia coli carrying mcr-1 among multiple environmental sources in rural China and associated risk to human health2019In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 251, p. 619-627Article in journal (Refereed)
    Abstract [en]

    Antibiotic resistance among gram-negative bacteria is increasingly becoming a problem of global concern. Particularly problematic is the emergence of resistance to last-resort antibiotics such as carbapenems and colistin. The increasing number of reports on the plasmid-mediated colistin resistance gene mcr-1 in isolates worldwide is raising concerns for the future usefulness of this class of antibiotics. Dissemination of mcr-1 is believed to have originated mainly from animal breeding, however, the role of the environment as a transmission source is not yet fully understood. In the current study, 89 extended spectrum beta-lactamase-producing Escherichia coli isolated from 231 samples from different environmental sources in 12 villages in a rural area of Shandong, China, were screened for mcr-1.17 (19.1%) mcr-1-positive isolates were found from different environmental sources, aggregated in 6 villages. Plasmids of three different Inc-groups carrying mcr-1 were confirmed, indicating that the widespread geographical distribution of mcr-1 in the local area is due to a number of different plasmids. Additionally, almost a third (29.4%) of the isolates carried virulence factors associated to intestinal pathogenic E. coli. These results illustrate the high complexity of the transmission patterns of mcr-1 among different environmental matrices on a local scale and the potential for the environment to facilitate dissemination and emergence of antibiotic-resistant and virulent strains of bacteria. (C) 2019 Elsevier Ltd. All rights reserved.

  • 24.
    KK, Sriram
    et al.
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Ekedahl, Elina
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Hoang, Ngoc Thi Bich
    Department of Microbiology, Vietnam National Children's Hospital, Hanoi, Vietnam.
    Sewunet, Tsegaye
    Division of Clinical Microbiology, Department of Laboratory medicine, Karolinska Institutet, Stockholm, Sweden.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Lundberg, Ludwig
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Nematzadeh, Shoeib
    Division of Clinical Microbiology, Department of Laboratory medicine, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Maud
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Le, Ngai Kien
    Department of Infection Control, Vietnam National Children's Hospital, Hanoi, Vietnam.
    Tran, Dien Minh
    Department of Surgery, Vietnam National Children's Hospital, Hanoi, Vietnam.
    Hanberger, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
    Olson, Linus
    Department of Global Public Health, Karolinska Institutet, Stockholm, Department of Women and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Mattias
    Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Giske, Christian G.
    Division of Clinical Microbiology, Department of Laboratory medicine, Karolinska Institutet, Stockholm, Clinical microbiology, Karolinska University Hospital, Stockholm, Sweden .
    Westerlund, Fredrik
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    High diversity of blaNDM-1-encoding plasmids in Klebsiella pneumoniae isolated from neonates in a Vietnamese hospital2022In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 59, no 2, article id 106496Article in journal (Refereed)
    Abstract [en]

    Objectives: The carbapenemase-encoding gene blaNDM-1 has been reported in Vietnam during the last 10 years, and blaNDM-producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of blaNDM-1 is plasmids, mobile genetic elements that commonly carry antibiotic resistance genes and spread via conjugation. The diversity of blaNDM-1-encoding plasmids from neonates at a large Vietnamese hospital was characterized in this study.

    Methods: 18 fecal Klebsiella pneumoniae and Klebsiella quasipneumoniae isolates collected from 16 neonates at a large pediatric hospital in Vietnam were studied using optical DNA mapping (ODM) and next-generation sequencing (NGS). Plasmids carrying the blaNDM-1 gene were identified by combining ODM with Cas9 restriction. The plasmids in the isolates were compared to investigate whether the same plasmid was present in different patients.

    Results: Although the same plasmid was found in some isolates, ODM confirmed that there were at least 10 different plasmids encoding blaNDM-1 among the 18 isolates, thus indicating wide plasmid diversity. The ODM results concur with the NGS data. Interestingly, some isolates had two distinct plasmids encoding blaNDM-1 that could be readily identified with ODM. The coexistence of different plasmids carrying the same blaNDM-1 gene in a single isolate has rarely been reported, probably because of limitations in plasmid characterization techniques.

    Conclusions: The plasmids encoding the blaNDM-1 gene in this study cohort were diverse and may represent a similar picture in Vietnamese society. The study highlights important aspects of the usefulness of ODM for plasmid analysis.

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  • 25.
    Lu, Dan
    et al.
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Xia, Yi
    Zhejiang Univ, Peoples R China.
    Jain, Ajay
    Indiana Univ Hlth, IN USA.
    Gu, Qing
    Zhejiang Univ, Peoples R China.
    Ji, Feng
    Zhejiang Univ, Peoples R China.
    Endoscopic removal of a massive trichobezoar in a pediatric patient by using a variceal ligator cap: A case report and literature review2022In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 9, article id 1020648Article, review/survey (Refereed)
    Abstract [en]

    A trichobezoar is commonly formed in the gastrointestinal tract by ingestion of an individuals own hair. A trichobezoar formed by hair and artificial materials constitutes a rare etiology scarcely reported in the current literature. A mixture with hair-like synthetic fibers not only increases the risk for trichobezoar formation but also makes it more difficult for endoscopic removal. Herein, we report on a case in which a trichobezoar, caused by the consumption of human hair and synthetic yarn, was successfully removed endoscopically with a variceal ligator cap without further complications for the patient. This case report aims to raise awareness among endoscopists that using a variceal ligator cap may be a suitable option in the management of large trichobezoars containing synthetic fibers.

  • 26.
    Lu, Dan
    et al.
    Zhejiang Univ, Peoples R China.
    Lv, Lu
    Zhejiang Univ, Peoples R China.
    Gu, Qing
    Zhejiang Univ, Peoples R China.
    Jain, Ajay
    Indiana Univ, IN 46204 USA.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Ji, Feng
    Zhejiang Univ, Peoples R China.
    Extraction of Fish Bones Embedded in the Esophagus via Endoscopic Submucosal Dissection: Two Case Reports and Literature Review2021In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 8, article id 746720Article, review/survey (Refereed)
    Abstract [en]

    Foreign body ingestion is a common problem encountered at gastroenterology clinics and emergency rooms which can cause serious complications. Usually, foreign bodies are directly visible with flexible endoscopes and can be readily removed. However, when foreign bodies migrate into the deeper tissue of the esophagus, surgery is typically required. There is currently no consensus regarding the best treatment. In this report, we present two cases in which fish bones embedded in the submucosal and muscularis propria of the esophagus were successfully removed via endoscopic submucosal dissection (ESD). Both patients were discharged without any complications.

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  • 27.
    Lu, Yanmeng
    et al.
    Zhejiang Univ, Peoples R China.
    Han, Shengyi
    Zhejiang Univ, Peoples R China.
    Zhang, Shuobo
    Zhejiang Univ, Peoples R China.
    Wang, Kaicen
    Zhejiang Univ, Peoples R China.
    Lv, Longxian
    Zhejiang Univ, Peoples R China.
    McClements, David Julian
    Univ Massachusetts, MA 01003 USA.
    Xiao, Hang
    Univ Massachusetts, MA 01003 USA.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Yao, Mingfei
    Zhejiang Univ, Peoples R China.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China.
    The role of probiotic exopolysaccharides in adhesion to mucin in different gastrointestinal conditions2022In: CURRENT RESEARCH IN FOOD SCIENCE, ISSN 2665-9271, Vol. 5, p. 581-589Article in journal (Refereed)
    Abstract [en]

    The presence of exopolysaccharides (EPS), a type of biomacromolecules, on the surface of probiotics play an important role in mucoadhesion, and it can be severely influenced by environments during gastrointestinal transit. In this study, the impact of gastrointestinal factors on surface properties of two probiotics (Lactobacillus rhamnosus GG and Pediococcus pentosaceus LI05) was investigated. Probiotic suspensions had relatively high viscosities and exhibited pronounced shear-thinning behavior due to the presence of EPS. The zeta-potential of both probiotics was relatively low and was not believed to play an important role in mucoadhesion. Compared to the control, the adhesive forces tended to decrease in the presence of gastric acids but increase in the presence of bile salts, since bile salts led to a thicker more open EPS layer compared to gastric acids. Although the functional groups of EPS in both probiotics are similar according to the study by FT-IR spectroscopy, the molecular weight of purified EPS in LI05 was much higher, ranging from 10,112 Da to 477,763 Da, which may contribute to higher rupture length in LI05 group. These results suggest that probiotic-mucin interactions are governed by the compositions and changes in the EPS of the probiotics in different gastrointestinal conditions, which contribute to a better understanding of the mucoadhesive behavior of the probiotics in the GIT.

  • 28.
    Luo, Qixia
    et al.
    Zhejiang Univ, Peoples R China.
    Wang, Yuan
    Zhejiang Univ, Peoples R China.
    Fu, Hao
    Zhejiang Univ, Peoples R China.
    Yu, Xiao
    Zhejiang Univ, Peoples R China.
    Zheng, Beiwen
    Zhejiang Univ, Peoples R China.
    Chen, Yunbo
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Xiao, Yonghong
    Zhejiang Univ, Peoples R China.
    Serotype Is Associated With High Rate of Colistin Resistance Among Clinical Isolates of Salmonella2020In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 11, article id 592146Article in journal (Refereed)
    Abstract [en]

    To investigate the prevalence, probable mechanisms and serotype correlation of colistin resistance in clinical isolates of Salmonella from patients in China, Salmonella isolates were collected from fecal and blood samples of patients. In this study, 42.8% (136/318) clinical isolated Salmonella were resistant to colistin. MIC distribution for colistin at serotype level among the two most prevalent serotypes originating from humans in China indicated that Salmonella Enteritidis (83.9% resistance, 125/149) were significantly less susceptible than Salmonella Typhimurium (15.3% resistance, 9/59, P < 0.01). mcr genes and mutations in PmrAB confer little for rate of colistin resistant Salmonella isolated from human patients. Phylogenetic tree based on core-genome single nucleotide polymorphisms (SNPs) was separately by the serotypes and implied a diffused distribution of MICs in the same serotype isolates. Relatvie expression levels of colistin resistant related pmr genes were significantly higher in non-mcr colistin resistant S. Typhimurium than in colistin sensitive S. Typhimurium, but no discernable differences between colistin resistant and sensitive S. Enteritidis, indicating a different mechanism between colistin resistant S. Typhimurium and S. Enteritidis. In conclusion, colistin susceptibility and colistin resistant mechanism of clinical isolated Salmonella were closely associated with specific serotypes, at least in the two most prevalent serotype Enteritidis and Typhimurium. We suggest clinical microbiology laboratory interpreting Salmonella colistin MIC results in the serotype level.

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  • 29.
    Qiu, Bo
    et al.
    Zhejiang Univ, Peoples R China.
    Zhu, Lian
    Hangzhou Med Coll, Peoples R China.
    Zhang, Shuobo
    Zhejiang Univ, Peoples R China.
    Han, Shengyi
    Zhejiang Univ, Peoples R China.
    Fei, Yiqiu
    Zhejiang Univ, Peoples R China.
    Ba, Furong
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China; Jinan Microecol Biomed Shandong Lab, Peoples R China.
    Yao, Mingfei
    Zhejiang Univ, Peoples R China.
    Prevention of Loperamide-Induced Constipation in Mice and Alteration of 5-Hydroxytryotamine Signaling by Ligilactobacillus salivarius Li012022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 19, article id 4083Article in journal (Refereed)
    Abstract [en]

    Although Ligilactobacillus salivarius Li01 (Li01) has shown much promise in preventing multiple gastrointestinal diseases, the potential of the probiotic in alleviating constipation and the related mechanisms remain unclear. In this study, the effects of Li01 were evaluated in a loperamide-induced constipation mouse model. The results demonstrated that Li01 intervention can relieve constipation symptoms by improving water content, quantity, and morphology of feces and act as an intestinal barrier structure protector. Furthermore, Li01 can modulate gut motility (gastrointestinal transit rate), the fluid transit-associated expression of aquaporins, and the serum parameters vasoactive intestinal peptide, substance P, and somatostatin. Constipation significantly increased the levels of 5-hydroxytryotamine (5-HT) in serum (p < 0.01) and decreased the levels in the intestine (p < 0.001). Due to its function of elevating the expression of tryptophan hydroxylase 1, this was reversed after Li01 treatment. Li01 also promoted the expression of 5-HT receptor 3 and 4, indicating that the 5-HT signaling pathway may play a critical role in the mechanism by which Li01 alleviate constipation symptoms. Additionally, Li01 significantly altered the gut microbiota composition by enhancing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Rikenellaceae_RC9 genera. Based on the above results, Li01 may have the potential to effectively alleviate constipation by regulating the 5-HT pathway and alteration of the gut microbiota.

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  • 30.
    Shen, Ping
    et al.
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Chen, Yong
    Jinan Univ, Peoples R China; Southern Univ Sci & Technol, Peoples R China.
    Zhou, Yanzi
    Zhejiang Univ, Peoples R China.
    Xiao, Tingting
    Zhejiang Univ, Peoples R China.
    Xiao, Yonghong
    Zhejiang Univ, Peoples R China.
    Zhou, Kai
    Jinan Univ, Peoples R China; Southern Univ Sci & Technol, Peoples R China.
    Hypervirulence Markers Among Non-ST11 Strains of Carbapenem- and Multidrug-ResistantKlebsiella pneumoniaeIsolated From Patients With Bloodstream Infections2020In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 11, article id 1199Article in journal (Refereed)
    Abstract [en]

    Multidrug-resistantKlebsiella pneumoniaeand hypervirulentK. pneumoniae(hvKP) have traditionally been considered two individual populations; however, strains displaying both phenotypes have emerged during the recent decade. Understanding the genotypic and phenotypic basis of the convergence could be of clinical importance. In this study, we aimed to evaluate the pathogenicity associated with different combinations of genotypes (i.e., sequence types, virulence factors, and capsular serotypes) and phenotypes (i.e., hypermucoviscosity and drug susceptibility) inK. pneumoniae.A total of 11K. pneumoniaeisolates causing bloodstream infections were included in the study, and they were assigned to seven STs (ST23, ST15, ST268, ST660, ST86, ST65, and ST1660) and carried various K-loci (KL1, KL2, KL16, KL20, and KL24). Hypermucoviscosity was observed for six isolates.bla(KPC-2)was detected in six carbapenem-resistant isolates, and the remaining ones were either multidrug-resistant or resistant to two types of antibiotics. Aerobactin- and yersiniabactin-encoding genes were detected in all isolates. AlthoughrmpA2was detected in all isolates, most contained frameshift mutations (82%). Genes encoding salmochelin, RmpA, and PEG344 were detected in seven isolates. Colibactin-encoding genes were carried by six isolates. Discrepancies among measured virulence inGalleria mellonellaand the serum-killing assay, and genotypes and phenotypes were detected. The results illustrate the complexity and difficulty with the current knowledge of hypervirulence to predict the phenotype by using genetic and phenotypic markers. Additionally, the emergence of carbapenem resistance in two isolates of KPC-2-producing hvKP of different sequence types emphasizes the urgency with which reliable clinical diagnostics for hvKP is needed.

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  • 31.
    Sun, Pan
    et al.
    Shandong University, Peoples R China.
    Bi, Zhenwang
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Zheng, Beiwen
    Zhejiang University, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Stalsby Lundborg, Cecilia
    Karolinska Institute, Sweden.
    Borjesson, Stefan
    National Vet Institute, Sweden.
    Li, Xuewen
    Shandong University, Peoples R China.
    Chen, Baoli
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Yin, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Occurrence of bla(KPC-2), bla(CTX-M), and mcr-1 in Enterobacteriaceae from Well Water in Rural China2017In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, no 4, article id e02569Article in journal (Refereed)
    Abstract [en]

    We report on the coexistence of mcr-1 and blaCTX-M in multidrugresistant, extended-spectrum beta-lactamase-producing Escherichia coli belonging to the sequence type 10 complex isolated from well water in rural China. Raoultella ornithinolytica with bla(KPC-2) was also detected in well water from the same area. This study shows that genes coding for resistance to last-resort antibiotics are present in wells in rural China, indicating a potential source of antibiotic resistance.

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  • 32.
    Wang, Y.
    et al.
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Zhu, Y.
    Zhejiang Univ, Peoples R China.
    Luo, Q.
    Zhejiang Univ, Peoples R China.
    Xiao, Y.
    Zhejiang Univ, Peoples R China.
    Performance of different methods for testing polymyxin B: comparison of broth microdilution, agar dilution and MIC test strip in mcr-1 positive and negative Escherichia coli2021In: Letters in Applied Microbiology, ISSN 0266-8254, E-ISSN 1472-765X, Vol. 73, no 2, p. 197-205Article in journal (Refereed)
    Abstract [en]

    Antimicrobial susceptibility testing with the last-resort antibiotics polymyxins (polymyxin B and colistin) is associated with several methodological issues. Currently, broth microdilution (BMD) is recommended for colistin and polymyxin B. BMD is laborious and the utility of alternative methods needs to be evaluated for polymyxin B susceptibility testing. In this study, using BMD as a reference method, the performance of agar dilution (AD) and MIC test strips (MTS) were evaluated in polymyxin B susceptibility testing. BMD, AD and MTS were used to determine MICs of 193 clinical isolates of Escherichia coli. Seventy-nine were positive for the polymyxin resistance gene mcr-1. Method performances were evaluated based on pair-wise agreements with the reference method (BMD) and statistical testing. AD and MTS showed an unacceptable number of very major errors (VMEs) compared with BMD, 9 center dot 3 and 10 center dot 7%, respectively. The essential agreement (EA) was low for AD (49 center dot 7%), but high for MTS (97 center dot 8%). However, statistical testing showed that MTS tended to yield a one-step lower MIC (P < 0 center dot 01) compared with BMD. The discordances observed with MTS and AD in comparison with BMD for polymyxin B susceptibility testing for E. coli suggest their inapplicability in routine testing. A large number of isolates clustered around the susceptibility breakpoint (2-4 mg l(-1)) and several mcr-1 positive isolates (17%) were determined as susceptible with BMD. A screening breakpoint for mcr-1 of 2 mg l(-1) should also be considered.

  • 33.
    Xiang, Ze
    et al.
    Zhejiang Univ, Peoples R China.
    Li, Jiayuan
    Zhejiang Univ, Peoples R China.
    Zhang, Zhengyu
    Nanjing Med Univ, Peoples R China.
    Cen, Chao
    Zhejiang Univ, Peoples R China.
    Chen, Wei
    Zhejiang Acad Tradit Chinese Med, Peoples R China.
    Jiang, Bin
    Cent Blood Stn Yancheng City, Peoples R China.
    Meng, Yiling
    Suzhou Vocat Hlth Coll, Peoples R China.
    Wang, Ying
    Nanjing Med Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Zhai, Guanghua
    Nanjing Med Univ, Peoples R China.
    Wu, Jian
    Nanjing Med Univ, Peoples R China.
    Comprehensive Evaluation of Anti-PD-1, Anti-PD-L1, Anti-CTLA-4 and Their Combined Immunotherapy in Clinical Trials: A Systematic Review and Meta-analysis2022In: Frontiers in Pharmacology, E-ISSN 1663-9812, Vol. 13, article id 883655Article, review/survey (Refereed)
    Abstract [en]

    Immunotherapy with immune checkpoint inhibitor (ICI) drugs is gradually becoming a hot topic in cancer treatment. To comprehensively evaluate the safety and efficacy of ICI drugs, we employed the Bayesian model and conducted a network meta-analysis in terms of progression-free survival (PFS), overall survival (OS) and severe adverse events (AEs). Our study found that treatment with ipilimumab was significantly worse than standard therapies in terms of PFS, whereas treatment with cemiplimab significantly improved PFS. The results also indicated that cemiplimab was the best choice for PFS. Treatment with nivolumab, pembrolizumab and nivolumab plus ipilimumab significantly improved OS compared to standard therapies. In terms of OS, cemiplimab was found to be the best choice, whereas avelumab was the worst. In terms of severe AEs, atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab all significantly reduced the risk of grade 3 or higher AEs compared to standard therapy. The least likely to be associated with severe AEs were as follows: cemiplimab, avelumab, nivolumab, atezolizumab, and camrelizumab, with nivolumab plus ipilimumab to be the worst. Therefore, different ICI drug therapies may pose different risks in terms of PFS, OS and severe AEs. Our study may provide new insights and strategies for the clinical practice of ICI drugs.

  • 34.
    Yang, Chengxia
    et al.
    Shandong Univ, Peoples R China.
    Han, Jingyi
    Shandong Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Zou, Huiyun
    Shandong Univ, Peoples R China.
    Gu, Congcong
    Shandong Univ, Peoples R China.
    Zhao, Ling
    Shandong Univ, Peoples R China.
    Meng, Chen
    Shandong Univ, Peoples R China.
    Zhang, Hui
    Shandong Univ, Peoples R China.
    Ma, Xianjun
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Dissemination of bla(NDM-5) and mcr-8.1 in carbapenem-resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae in an animal breeding area in Eastern China2022In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 13, article id 1030490Article in journal (Refereed)
    Abstract [en]

    Animal farms have become one of the most important reservoirs of carbapenem-resistant Klebsiella spp. (CRK) owing to the wide usage of veterinary antibiotics. "One Health"-studies observing animals, the environment, and humans are necessary to understand the dissemination of CRK in animal breeding areas. Based on the concept of "One-Health," 263 samples of animal feces, wastewater, well water, and human feces from 60 livestock and poultry farms in Shandong province, China were screened for CRK. Five carbapenem-resistant Klebsiella pneumoniae (CRKP) and three carbapenem-resistant Klebsiella quasipneumoniae (CRKQ) strains were isolated from animal feces, human feces, and well water. The eight strains were characterized by antimicrobial susceptibility testing, plasmid conjugation assays, whole-genome sequencing, and bioinformatics analysis. All strains carried the carbapenemase-encoding gene bla(NDM-5), which was flanked by the same core genetic structure (IS5-bla(NDM-5)-ble(MBL)-trpF-dsbD-IS26-ISKox3) and was located on highly related conjugative IncX3 plasmids. The colistin resistance gene mcr-8.1 was carried by three CRKP and located on self-transmissible IncFII(K)/IncFIA(HI1) and IncFII(pKP91)/IncFIA(HI1) plasmids. The genetic context of mcr-8.1 consisted of IS903-orf-mcr-8.1-copR-baeS-dgkA-orf-IS903 in three strains. Single nucleotide polymorphism (SNP) analysis confirmed the clonal spread of CRKP carrying-bla(NDM-5) and mcr-8.1 between two human workers in the same chicken farm. Additionally, the SNP analysis showed clonal expansion of CRKP and CRKQ strains from well water in different farms, and the clonal CRKP was clonally related to isolates from animal farms and a wastewater treatment plant collected in other studies in the same province. These findings suggest that CRKP and CRKQ are capable of disseminating via horizontal gene transfer and clonal expansion and may pose a significant threat to public health unless preventative measures are taken.

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  • 35.
    Yao, Mingfei
    et al.
    Zhejiang Univ, Peoples R China.
    Fei, Yiqiu
    Zhejiang Univ, Peoples R China.
    Zhang, Shuobo
    Zhejiang Univ, Peoples R China.
    Qiu, Bo
    Zhejiang Univ, Peoples R China.
    Zhu, Lian
    Hangzhou Med Coll, Peoples R China.
    Li, Fang
    Columbia Univ, NY 10032 USA.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Xiao, Hang
    Univ Massachusetts, MA 01003 USA.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China; Jinan Microecol Biomed Shandong Lab, Peoples R China.
    Gut Microbiota Composition in Relation to the Metabolism of Oral Administrated Resveratrol2022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 5, article id 1013Article in journal (Refereed)
    Abstract [en]

    Resveratrol (RSV) has been confirmed to confer multiple health benefits, and the majority of RSV tends to be metabolized in the gut microbiota after oral administration. In this study, the metabolism of RSV was investigated by using mouse models with distinct gut microbiota compositions: germ-free mice colonized with probiotics, conventional mouse, and DSS-induced colitis mouse models. The results demonstrated that in feces, the metabolites of RSV, including resveratrol sulfate (RES-sulfate), resveratrol glucuronide (RES-glucuronide), and dihydroresveratrol, significantly increased after probiotics colonized in germ-free mice. Furthermore, RES-sulfate and RES-glucuronide were below the detectable limit in the feces of conventional mice, with dihydroresveratrol being the dominant metabolite. Compared to the conventional mice, the ratio of Firmicutes/Bacteroides and the abundance of Lactobacillus genera were found significantly elevated in colitis mice after long-term ingestion of RSV, which shifted the metabolism of RSV in return. Our study provided critical implications in further application of RSV in foods and food supplements.

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  • 36.
    Yao, Mingfei
    et al.
    Zhejiang Univ, Peoples R China.
    Lu, Yanmeng
    Zhejiang Univ, Peoples R China.
    Zhang, Ting
    Zhejiang Univ, Peoples R China.
    Xie, Jiaojiao
    Zhejiang Univ, Peoples R China.
    Han, Shengyi
    Zhejiang Univ, Peoples R China.
    Zhang, Shuobo
    Zhejiang Univ, Peoples R China.
    Fei, Yiqiu
    Zhejiang Univ, Peoples R China.
    Ling, Zongxin
    Zhejiang Univ, Peoples R China.
    Wu, Jingjing
    Zhejiang Univ, Peoples R China.
    Hu, Yue
    Zhejiang Univ, Peoples R China.
    Ji, Shouling
    Zhejiang Univ, Peoples R China.
    Chen, Hao
    Chinese Acad Sci, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China.
    Improved functionality of Ligilactobacillus salivarius Li01 in alleviating colonic inflammation by layer-by-layer microencapsulation2021In: npj Biofilms and Microbiomes, E-ISSN 2055-5008, Vol. 7, no 1, article id 58Article in journal (Refereed)
    Abstract [en]

    The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (similar to 10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies.

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  • 37.
    Yao, Mingfei
    et al.
    Zhejiang Univ, Peoples R China.
    Qv, Lingling
    Zhejiang Univ, Peoples R China.
    Lu, Yanmeng
    Zhejiang Univ, Peoples R China.
    Wang, Baohong
    Zhejiang Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Li, Lanjuan
    Zhejiang Univ, Peoples R China.
    An Update on the Efficacy and Functionality of Probiotics for the Treatment of Non-Alcoholic Fatty Liver Disease2021In: Engineering, ISSN 2095-8099, Vol. 7, no 5, p. 679-686Article, review/survey (Refereed)
    Abstract [en]

    Non-alcoholic fatty liver disease (NAFLD), which has a global prevalence of 20%-33%, has become the main cause of chronic liver disease. Except for lifestyle medication, no definitive medical treatment has been established so far, making it urgent to find effective strategies for the treatment of NAFLD. With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD, studies on probiotics for the prevention and treatment of NAFLD are increasing in number. Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics. More recently, emerging next-generation probiotics (NGPs) such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD. This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD. The mechanisms by which probiotics directly or indirectly affect the disease are illustrated, based on the most recent animal and clinical studies. Although numerous studies have been published on this topic, further research is required to comprehensively understand the specific underlying mechanisms among probiotics, gut microbiota, and NAFLD, and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD, as well as the safety of probiotics in the human body. (C) 2020 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company.

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  • 38.
    Zhao, Qian
    et al.
    Shandong Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Zou, Huiyun
    Shandong Univ, Peoples R China.
    Zhou, Ziyu
    Shandong Univ, Peoples R China.
    Xia, Huiyu
    Shandong Univ, Peoples R China.
    Zhao, Ling
    Shandong Univ, Peoples R China.
    Nilsson, Lennart E
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Dissemination of bla(NDM-5) via IncX3 plasmids in carbapenem-resistant Enterobacteriaceae among humans and in the environment in an intensive vegetable cultivation area in eastern China2021In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 273, article id 116370Article in journal (Refereed)
    Abstract [en]

    The environment of a large-scale vegetable production area can be exposed to antibiotic residues and antibiotic-resistant bacteria (ARB) via animal manure and irrigation with contaminated water, which can facilitate the dissemination of ARB. However, the occurrence of ARB in plantation areas and their dissemination in this environment remain largely unexplored. In total, 382 samples including those from vegetable (n = 106), soil (n = 87), well water (n = 24), river water (n = 20), river sediments (n = 20), farmer feces (n = 58) and farmer hands (n = 67) were collected in 2019 from a large-scale cultivation area in Shandong, China. Selective agar plates were used to screen for carbapenem-resistant Enterobacteriaceae (CRE) and whole-genome sequencing and Southern blotting were used to characterise isolates and mobile genetic elements carrying carbapenem resistance determinants. A total of nine NDM-5-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Citrobacter spp. were identified from environmental sources and human feces, all of which were multidrug-resistant. Single nucleotide polymorphism analysis suggested clonal transmission of carbapenem-resistant Citrobacter sedlakii within greenhouse soils in the area. Eight of the isolates carried closely related or identical IncX3 plasmids carrying bla(NDM-5), which were shown to be conjugative via filter mating experiments, indicating the highly transmissible nature of this genetic element. Isolates of E. coli and Citrobacter freundii were detected in the feces of local farm workers and contained similar IncX3 plasmids with bla(NDM-5) environmental isolates, suggesting a potential risk of CRE transfer from the work environment to the farm workers. Thus, further research is required to investigate the potential health risks associated with environmental exposure to CRE in vegetable cultivation areas. (C) 2020 Elsevier Ltd. All rights reserved.

  • 39.
    Zhou, Ziyu
    et al.
    Shandong Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Liu, Jiaqi
    Shandong Univ, Peoples R China.
    Zhao, Ling
    Shandong Univ, Peoples R China.
    Xia, Huiyu
    Shandong Univ, Peoples R China.
    Zou, Huiyun
    Shandong Univ, Peoples R China.
    Zhao, Qian
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Emergence of IncX3 Plasmid-Harboring bla(NDM-5) in a Citrobacter sedlakii Isolated from Outdoor Aerosol in Wastewater Treatment Plant2022In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 28, no 2, p. 199-204Article in journal (Refereed)
    Abstract [en]

    A carbapenem-resistant Citrobacter sedlakii strain AA2CS carrying bla(NDM-5) was detected in outdoor aerosols of a wastewater treatment plant (WWTP) in China and the whole genome was sequenced subsequently. AA2CS was captured in an aerobic tank with aerosol particles of sizes ranging from 4.7 to 7.0 mu m. Besides bla(NDM-5), AA2CS also harbored 21 other antibiotic resistance genes and displayed a high level of resistance to ampicillin, cefotaxime, ceftazidime, tetracycline, and meropenem. Bla(NDM-5) was located on the IncX3 plasmid (pCSNDM-5) with an IS3000-IS5-bla(NDM-5)-ble(MBL)-trpF-dsbD-IS26 structure. pCSNDM-5 was highly homologous to other bla(NDM-5)-carrying IncX3 plasmids in China and can be transferred to the Escherichia coli recipient J53. To our knowledge, this is the first report of carbapenem-resistant Enterobacteriaceae in outdoor aerosols in WWTPs.

  • 40.
    Zou, Huiyun
    et al.
    Shandong Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Wang, Shuang
    Shandong Ctr Dis Control & Prevent, Peoples R China.
    Zhou, Ziyu
    Shandong Univ, Peoples R China.
    Gu, Congcong
    Shandong Univ, Peoples R China.
    Zhao, Ling
    Shandong Univ, Peoples R China.
    Meng, Chen
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Emergence of bla(NDM-1), bla(NDM-5), bla(KPC-2) and bla(IMP-4) carrying plasmids in Raoultella spp. in the environment2022In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 306, article id 119437Article in journal (Refereed)
    Abstract [en]

    To date, carbapenem-resistant Enterobacteriaceae have been found predominantly in clinical settings worldwide. Raoultella belongs to the Enterobacteriaceae family which can cause hospital-acquired infections, and carbapenem-resistant Raoultella spp. (CRR) is sporadically reported in the environment. We investigated the distribution and underlying resistance mechanisms of CRR in a wastewater treatment plant (WWTP) from eastern China between January 2018 and February 2019. A total of 17 CRR were isolated from 324 environmental samples, including Raoultella ornithinolytica (n = 15) and Raoultella planticola (n = 2). The detection of CRR was more frequent in the water inlet compared to anaerobic tank, aerobic tank, sludge thickener, activated sludge, mud cake storage area, and water outlet, and CRR was detected in mud cake stacking area. All CRR were resistant to imipenem, meropenem, ampicillin, piperacillin-tazobactam, cefotaxime, ceftazidime, trimethoprim-sulfamethoxazole and fosfomycin. Four different carbapenemase genes were identified, including bla(KPC-2) (n = 13), bla(NDM-1) (n = 8), bla(NDM-5) (n = 1), bla(IMP-4) (n = 1). Interestingly, isolated R. ornithinolytica from the WWTP were closely related to those reported from human samples in China. Plasmid analysis indicated that IncFII(Yp), IncP6, and IncU mediated bla(KPC-2) spread, IncX3 and IncN2 mediated bla(NDM) spread in the environment. The core structure of the Tn3-ISKpn27-bla(KPC-2)-ISKpn6, ISAba125-bla(NDM)-ble(MBL)-trpF-dsbD were identified. The study provides evidence that Raoultella spp. may spread alarming carbapenem resistance in the environment and, therefore, the continuous surveillance for carbapenem resistance in the WWTP should be conducted, especially sludge.

  • 41.
    Zou, Huiyun
    et al.
    Shandong Univ, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Xu, Hao
    Zhejiang Univ, Peoples R China.
    Chi, Xiaohui
    Shandong Univ, Peoples R China; Zhejiang Univ, Peoples R China.
    Zhao, Qian
    Shandong Univ, Peoples R China.
    Zhou, Ziyu
    Shandong Univ, Peoples R China.
    Xia, Huiyu
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Zheng, Beiwen
    Zhejiang Univ, Peoples R China.
    Genetic characterization and virulence of a carbapenem-resistant Raoultella ornithinolytica isolated from well water carrying a novel megaplasmid containing bla(NDM-1)2020In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 260, article id 114041Article in journal (Refereed)
    Abstract [en]

    Infections caused by carbapenem-resistant Enterobacteriaceae are a growing concern worldwide. Raoultella ornithinolytica is a species in the Enterobacteriaceae family which can cause hospital-acquired infections and is sporadically reported as carbapenem-resistant from human and environmental sources. In this study, we firstly report on an NDM-1-producing R. ornithinolytica, Rao166, isolated from drinking water in an animal cultivation area in China. In addition to carbapenem-resistance, Rao166 was resistant to several other antibiotics including gentamicin, sulfamethoxazole-trimethoprim, tetracycline and fosfomycin. Rao166 carried a novel IncFIC-type megaplasmid, 382,325 bp in length (pRAO166a). A multidrug resistance region, 60,600 bp in length, was identified in the plasmid containing an aac(3)-IId-like gene, aac(6)-Ib-cr, bla(DHA-1),bla(TEM-1B), bla(OXA-M-3), bla(NDM-1), qnrB4, catB3, arr-3, sul1, and tet(D). Results from virulence assays implied that Rao166 has considerable pathogenic potential. Although pRAO166a was found to be non-transmissible, dissemination of the NDM-1 producing strain may occur from well water to humans or animals through cross-contamination during food preparation or directly via drinking water, and potentially lead to difficult-to-treat infections. Thus, contamination of well water by this carbapenem-resistant and presumptively virulent strain of R. ornithinolytica should be considered a potential public health risk. (C) 2020 Elsevier Ltd. All rights reserved.

  • 42.
    Zou, Huiyun
    et al.
    Shandong Univ, Peoples R China.
    Zheng, Beiwen
    Zhejiang Univ, Peoples R China.
    Sun, Mingli
    Ctr Dis Prevent and Control, Peoples R China.
    Ottoson, Jakob
    Natl Food Agcy, Sweden.
    Li, Yubo
    Ctr Dis Prevent and Control, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Zhejiang Univ, Peoples R China.
    Chi, Xiaohui
    Shandong Univ, Peoples R China.
    Ji, Xiang
    Shandong Univ, Peoples R China.
    Li, Xuewen
    Shandong Univ, Peoples R China.
    Lundborg, Cecilia Stalsby
    Karolinska Inst, Sweden.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Evaluating Dissemination Mechanisms of Antibiotic-Resistant Bacteria in Rural Environments in China by Using CTX-M-Producing Escherichia coli as an Indicator2019In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 25, no 7, p. 975-984Article in journal (Refereed)
    Abstract [en]

    It is becoming increasingly recognized that the environment plays an important role both in the emergence and in dissemination of antibiotic-resistant bacteria (ARB), Mechanisms and factors facilitating this development are, however, not yet well understood. The high detection rate of CTX-M genes in environmental sources provides an opportunity to explore this issue. In this study, 88 CTX-M-producing Escherichia coli were isolated from 30 pig feces samples from 30 pig farms and 201 environmental samples. CTX-M-producing E. coli was detected with the following frequencies in the different types of samples: pig feces, 73%; river water, 64%; river sediment, 52%; wastewater, 31%; drinking water, 23%; outlet sediment, 21%; soil, 17%; and vegetables, 4.4%. Dissemination of CTX-M-producing E. coli to different environmental matrices was evaluated by analyzing the genetic relatedness of isolates from different environmental sources, and putative transmission routes through bird feces, pig feces, drinking water, river sediment, river water, and wastewater were hypothesized. Dissemination through these routes is likely facilitated by anthropogenic activities and environmental factors. Wild birds as potential vectors for dissemination of CTX-M-producing E. coli have the capacity to spread ARB across long distances. Regional dissemination between different environmental matrices of CTX-M-producing E. coli increases the exposure risk of humans and animals in the area.

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    Evaluating Dissemination Mechanisms of Antibiotic-Resistant Bacteria in Rural Environments in China by Using CTX-M-Producing Escherichia coli as an Indicator
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