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Increased endothelial activation in neonatal sepsis isolates of Staphylococcus epidermidis, but no differences in biofilm producing properties between sepsis and contaminant isolates
Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Staphylococcus epidermidis is the predominating etiological agent in neonatal septicemia today, but specific specific factors associated with S. epidermidis are incompletely described. We compared neonatal blood isolates of S. epidermidis representing sepsis (n = 12) or skin contaminants (n = 38) regarding endothelial activation, and the prevalence of genes encoding for biofilm production (icaAB and D), fibrinogen-binding protein (fbe) and methicillin resistance (mecA).

Endothelial cells cultured from human umbilical veins (HUVEC) were challenged by the different isolates of S. epidermidis. Endothelial release of adhesion molecules and interleukin-8 (IL-8) was investigated by an ELISA. Endothelial cell death was determined by light microscopy. The different genes were detected by PCR, and phenotypic biofilm production was investigated by Trypan blue staining. The sepsis isolates of S. epidermidis induced significantly higher endothelial release of intracellular adhesion molecule 1 (ICAM-1, p = 0.0021), endothelial selectin (E-selectin, p = 0.002), and IL-8 (p = 0.010) compared to the contaminants. Vaseular cell adhesion molecules 1 (VCAM-1) was not released. The sepsis-isolates were more cytotoxic than the contaminants; Nine out of 12 sepsis strains induced ≥ 50% cytotoxicity to HUVEC, compared to 15/38 contaminant strains (p = 0.047). The prevalence of the ica-operon, biofilm-production, fbe-, or mecA genes did not discriminate between sepsis and contaminant isolates. It is concluded that sepsis isolates of S. epidermidis induced higher endothelial release of chemotactic inflammatory mediators compared to contaminant isolates, but that the production of biofilm might be less important in neonatal infections eaused by S. epidermidis.

National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-85068OAI: diva2:564054
Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2012-11-01
In thesis
1. Coagulase-negative staphylococci septicaemia in newborns: aspects on host-bacterial interactions with special regard to neutrophil and endothelial response
Open this publication in new window or tab >>Coagulase-negative staphylococci septicaemia in newborns: aspects on host-bacterial interactions with special regard to neutrophil and endothelial response
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Newborn infants, especially those born preterm, are immunologically immature and prone to invasive infections. As a result of the increasing survival of very preterm (VPT < 31 weeks gestational age) newborns, nosocomial septicaemia has become a major concern the neonatal intensive care, and coagulase-negative staphylococci (CoNS) are nowadays the most frequently isolated pathogens in neonatal blood cultures. Further insight into host-bacterial interactions is required for the development of preventive strategies against CoNS septicaemia in VPT newborns.

Aim of the study: To investigate host-bacterial interactions in neonatal CoNS septicaemia with special regard to the neutrophil and endothelial response and to bacterial virulence factors.

Methods and results: Neonatal blood isolates of CoNS collected at Örebro University Hospital, Örebro, Sweden during the years 1983-1997 were characterised clinically and according to species and to phenotypic and genotypic patterns. Biochemial fingerprinting was found useful as a screening tool for selection of phenotypically related strains, but for further discrimination within a phenotypic cluster, genetic fingerprinting by pulsed field gel electrophoresis (PFGE) was required.

The isolates of S. epidermidis collected during the later part of the study period (1990-1997, n = 50) were further investigated. A hypervirulent clone of bacteria was identified, representing 7 of the 12 sepsis isolates in that cohort. These 12 isolates of S. epidermidis induced significantly higher endothelial release of neutrophil chemoattractants from human umbilical vein endothelial cell (HUVEC) cultures than did the isolates regarded as skin contaminants (n = 38). There were no differences between the sepsis and contaminant groups in the prevalence of genes for biofilm production, methicillin resistance or fibrinogen-binding protein.

The neutrophil oxidative burst occuring after stimulation by different bacterial strains was investigated by a flow cytometric method applied to a whole blood model. The oxidative activity in unstimulated neutrophils was similar in term (n = 10) and preterm (n = 10) newborns. However, the term newborns showed a significantly higher capacity to up-regulate the oxidative burst after bacterial stimulation. Significant differences in oxidative responses to different bacterial strains were observed, but these differences could not be related exclusively to species or invasive capacity.

A neutrophil granule protein, human neutrophil lipocalin (HNL), was evaluated as an early marker of neonatal septicaemia in newborns with clinical signs of infection. The serum level of HNL was significantly higher in the infected group of neonates (n = 25) than in the group with non-proven infection (n = 62). In healthy term controls the HNL level was similar at age 3 days to that at birth and close to the level reported in healthy adults.

Conclusions: The increased up-regulation of endothelial inflammatory mediators induced by sepsis isolates of S. epidermidis represents an important step in the pathogenesis of neonatal CoNS septicaemia. HNL might be useful as a marker of neutrophil activity also in VPT newborns. The laboratory assays used in the present study can be further developed for future investigations of the pathogenesis and host-bacterial interactions in neonatal CoNS septicaemia.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2004. 70 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 861
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-22100 (URN)1194 (Local ID)91-7373-836-0 (ISBN)1194 (Archive number)1194 (OAI)
Public defence
2004-10-15, B-husets aula, Universitetssjukhuset, Örebro, 09:00 (Swedish)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-11-01Bibliographically approved

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Björkqvist, Maria
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