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Staphylococcus aureus: aspects of pathogenesis and molecular epidemiology
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Staphylococcus aureus is a human commensal colonizing about 30 per cent of the population. Besides, it is a frequent cause of infections such as skin, wound and deep tissue infections and also more life-threatening conditions such as pneumonia, endocarditis and septicaemia. S. aureus may also cause different toxicoses. Moreover, this bacterium is one of the most common causes of nosocomial infections worldwide and an increase in antibiotic resistance, especially against methicillin, is seen. This underlines the importance to prevent and control outbreaks of S. aureus. The aims of this thesis were to increase the knowledge of S. aureus virulence and pathogenesis as well as to understand pattern of colonization and transmission.

Various virulence factors operate together in the pathogenic process of S. aureus. The virulence of S. aureus was studied by the interaction with human umbilical vein endothelial cells (HUVEC) as a model. In paper I, we found that one bacterial isolate survived intracellularly and that 156 genes were differentially regulated in microarray analysis of HUVEC. The major part of these genes coded for proteins involved in innate immunity. In paper II, we wanted to explore possible differences in global gene expression patterns in HUVEC induced by invasive compared to colonizing isolates of S. aureus. We also used microarray to investigate possible differences in the presence of virulence genes between the two groups. The main finding was that virulent and commensal S. aureus did not differ in interaction with HUVEC and in the presence of virulence genes. All isolates survived intracellularly for days.

Since no obvious differences in virulence between the two groups of isolates were found, we focused on epidemiology and transmission patterns. Colonization with S. aureus is an important risk factor for subsequent S. aureus infection. In paper III, we investigated S. aureus colonization and transmission among nursing home residents in three regions in the south of Sweden and used staphylococcal protein A (spa) typing as an epidemiological tool. A diverse distribution of different spa types was found and a majority of types were unique to one individual. Interestingly, we found a local accumulation of one spa type in one nursing home. Also common spa types were equally distributed in the different regions. We also noted that some individuals were colonized with two different spa types of S. aureus and in five of these cases there was one resistant and one non-resistant strain.

The issue of multiclonal colonization and infection is highly important and clinical diagnostic laboratories do not routinely address this problem. Therefore, in paper IV a novel method to assess multiclonality of S. aureus was developed. It was based on denaturing gradient gel electrophoresis with the amplification of the spa gene. The method simultaneously separated eight different spa types. It also detected two spa types in an outbreak.

In conclusion, we found no differences in virulence genes and in the interaction with HUVEC between commensal and invasive isolates. This indicates that any isolate of S. aureus might have a pathogenic potential. We also confirmed that some spa types are more successful colonizers with a potential to nosocomial spread. The method for detection of multiclonality of S. aureus is of importance in future epidemiological and clinical studies.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. , 78 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1371
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-97343ISBN: 978-91-7519-568-1 (print)OAI: oai:DiVA.org:liu-97343DiVA: diva2:647005
Public defence
2013-09-27, Originalet, Qulturum, Länssjukhuset Ryhov, Jönköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2013-09-10 Created: 2013-09-10 Last updated: 2013-09-12Bibliographically approved
List of papers
1. Infection of human endothelial cells with Staphylococcus aureus induces transcription of genes encoding an innate immunity response
Open this publication in new window or tab >>Infection of human endothelial cells with Staphylococcus aureus induces transcription of genes encoding an innate immunity response
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2005 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, no 6, 536-544 p.Article in journal (Refereed) Published
Abstract [en]

Staphylococcus aureus is a gram-positive bacterium frequently isolated from patients with bloodstream infections. Endothelial cells (EC) play an important role in host defence against bacteria, and recent reports have shown that infection of EC with S. aureus induces expression of cytokines and cell surface receptors involved in activating the innate immune response. The ability of S. aureus to invade nonphagocytic cells, including EC, has been documented. However, the knowledge of the role of EC in pathogenesis of S. aureus infection is still limited. In this study, we investigate the gene-expression program in human EC initiated by internalized 5. aureus, using microarray analysis. We found 156 genes that were differentially regulated at least threefold, using arrays representing 14,239 genes. Many of the up regulated genes code for proteins involved in innate immunity, such as cytokines, chemokines and cell adhesion proteins. Other upregulated genes encode proteins involved in antigen presentation, cell signalling and metabolism. Furthermore, intracellular bacteria survived for days without inducing EC death. © 2005 Blackwell Publishing Ltd.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28868 (URN)10.1111/j.1365-3083.2005.01597.x (DOI)14062 (Local ID)14062 (Archive number)14062 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
2. Staphylococcus aureus isolates from blood and anterior nares induce similar innate immune responses in endothelial cells
Open this publication in new window or tab >>Staphylococcus aureus isolates from blood and anterior nares induce similar innate immune responses in endothelial cells
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2009 (English)In: APMIS, ISSN 0903-4641, Vol. 117, no 11, 814-824 p.Article in journal (Refereed) Published
Abstract [en]

To evaluate the possibility to distinguish virulent from non-virulent isolates, gene expression in human umbilical vein endothelial cells (HUVEC) induced by invasive and colonizing isolates of Staphylococcus aureus was compared. Gene expression in HUVEC was analyzed by microarray analysis after 4 h of infection with Staphylococcus aureus, isolated from healthy nasal carriers (n = 5) and from blood of septic patients (n = 5), to explore possible differences between the groups of bacteria in interaction with HUVEC. All isolates were spa-typed to disclose strain relatedness. Moreover, the isolates were characterized with DNA microarray to determine the presence of virulence genes and to investigate the potential genes of importance in HUVEC interaction. The expression of 41 genes was up-regulated, and four were down-regulated in HUVEC by all isolates. Most of the up-regulated genes encode cytokines, chemokines, interferon-induced proteins, proteins regulating apoptosis and cell proliferation. There was no difference in the gene expression pattern between HUVEC infected with invasive or colonizing isolates. Furthermore, there was no difference in the presence of bacterial virulence genes between the two groups. In conclusion, our data indicate that S. aureus isolates induce comparable expression patterns in HUVEC, irrespective of invasiveness or presence of virulence genes.

Keyword
Staphylococcus aureus, HUVEC, infection, gene expression, virulence
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-51487 (URN)10.1111/j.1600-0463.2009.02535.x (DOI)
Available from: 2009-11-04 Created: 2009-11-04 Last updated: 2014-01-16Bibliographically approved
3. Prevalence and molecular epidemiology of Staphylococcus aureus in Swedish nursing homes – as revealed in the SHADES study
Open this publication in new window or tab >>Prevalence and molecular epidemiology of Staphylococcus aureus in Swedish nursing homes – as revealed in the SHADES study
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2014 (English)In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, no 6, 1310-1316 p.Article in journal (Refereed) Published
Abstract [en]

Knowledge of carriage and population dynamics of Staphylococcus aureus is crucial for infection risk assessment and to reveal transmission patterns of strains. We report the prevalence and molecular epidemiology of S. aureus in elderly people (n = 290) living in nursing homes in three cities in the south of Sweden. The overall carriage prevalence rate was 48% when results from nares (31%) and throat (34%) samples were combined. Common spa types were equally distributed but a frequent type, t160, was found only in one of the regions. Carriage of different spa types was detected in 23% of individuals and antimicrobial resistance rates were higher in S. aureus isolates from those carrying more than one spa type. Five of the 21 individuals who carried different spa types were colonized simultaneously with resistant and non-resistant strains. Seventeen per cent of the individuals carried S. aureus of the same spa type on all occasions. Methicillin resistance was not detected. In conclusion we found a high prevalence of S. aureus in this elderly population with a high rate of dual colonization with different spa types. We also found signs of institutional spread of one strain.

Place, publisher, year, edition, pages
Cambridge University Press, 2014
Keyword
Colonization, molecular typing, multiclonality, nursing home, spa type
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-97342 (URN)10.1017/S0950268813002033 (DOI)000334247600020 ()23962597 (PubMedID)
Available from: 2013-09-10 Created: 2013-09-10 Last updated: 2017-12-06Bibliographically approved
4. Analyzing Multiclonality of Staphylococcus aureus in Clinical Diagnostics Using spa-Based Denaturing Gradient Gel Electrophoresis
Open this publication in new window or tab >>Analyzing Multiclonality of Staphylococcus aureus in Clinical Diagnostics Using spa-Based Denaturing Gradient Gel Electrophoresis
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2011 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 49, no 10, 3647-3648 p.Article in journal (Refereed) Published
Abstract [en]

We present a novel denaturing gradient gel electrophoresis (DGGE) method which characterizes multiclonal communities of Staphylococcus aureus. The spa PCR-based DGGE method simultaneously separates strains that differ in only one base, thereby revealing multiclonal colonization and infections.

Place, publisher, year, edition, pages
American Society for Microbiology, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71642 (URN)10.1128/JCM.00389-11 (DOI)000295360700034 ()
Note
Funding Agencies|Swedish Society of Medicine||Futurum||Research Council of South-East Sweden (FORSS)||Available from: 2011-10-27 Created: 2011-10-27 Last updated: 2017-12-08

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