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Détection et mécanismes moléculaires de la résistance aux glycopeptides chez les staphylocoques dorés

English title Detection and molecular mechanisms of glycopeptide resistance in Staphylococcus aureus
Applicant Lew Daniel
Number 108401
Funding scheme Project funding (Div. I-III)
Research institution Service des Maladies Infectieuses Département de Médecine Interne Hôpital Cantonal - HUG
Institution of higher education University of Geneva - GE
Main discipline Medical Microbiology
Start/End 01.05.2005 - 31.10.2008
Approved amount 320'120.00
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All Disciplines (2)

Medical Microbiology
Infectious Diseases

Keywords (6)

methicillin-resistant Staphylococcus aureus; MRSA glycopeptide resistance; vancomycin; teicoplanin; glycopeptide-intermediate; Staphylococcus aureus

Lay Summary (English)

Lay summary
Methicillin-resistant Staphylococcus aureus (MRSA) are major pathogens of hospital-acquired and more recently community-acquired infections. Antibiotic therapy of patients infected with hospital-acquired MRSA strains, which are frequently resistant to most other antibiotics, generally requires parenteral administration of glycopeptide antibiotics, namely vancomycin or teicoplanin. Intensive use of vancomycin or teicoplanin potentially leads to the selection of MRSA isolates displaying low-level intermediate (GISA) or high (VRSA) levels of resistance to glycopeptides. Clinical GISA isolates represent a special risk because the molecular mechanisms underlying resistance are endogenous and poorly understood, and phenotypic detection of such isolates is particularly difficult.Emergence of glycopeptide resistance is currently viewed as the progressive selection of subpopulations of GISA precursors by long-term glycopeptide therapy, eventually leading to homogeneous GISA populations. GISA are generally characterized by cell wall thickening that seem to result from multiple genomic changes altering in an unknown manner transcription of several cell-wall regulation pathways.We want to identify by transcription profiling and genetic methods specific genes and metabolic pathways playing a key role in emergence of glycopeptide resistance in S. aureus. Based on new knowledge obtained from the mechanistic studies of gene expression we want to develop a simplified, reliable assay for targeted screening of putative GISA isolates that can be exploited in a clinical microbiological laboratory both for clinical and epidemiological studies. Improved understanding of the molecular mechanisms of endogenous glycopeptide resistance may help to: (i) find out potential targets for molecular screening and diagnostic of resistant isolates; (ii) unravel novel targets for development of local or systemic antibiotics. The successful development of a simplified detection assay of GISA will provide a powerful and timely tool for epidemiological detection and development of strategies for prevention of antimicrobial resistance, and for evaluating the impact of glycopeptide resistance on the outcome of glycopeptide therapy.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants


Associated projects

Number Title Start Funding scheme
121418 Ultra High Throughput sequencing platform for functional genome analysis 01.08.2008 R'EQUIP
125109 Mécanismes moléculaires de la resistance intermédiaire aux glycopeptides chez les staphyloques dorés 01.07.2009 Project funding (Div. I-III)