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Glycopeptide Resistance in Staphylococcus aureus: Emergence and Impact on Bacterial Virulence Assessed by in Vivo Studies Coupled to Functional Genomics

Applicant Vaudaux Pierre
Number 63250
Funding scheme NRP 49 Antibiotic resistance
Research institution Service des Maladies Infectieuses Département de Médecine Interne Hôpital Cantonal - HUG
Institution of higher education University of Geneva - GE
Main discipline Infectious Diseases
Start/End 01.10.2001 - 30.09.2004
Approved amount 400'099.00
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Lay Summary (English)

Lead
Lay summary
Glycopeptide resistance in Staphylococcus aureus: emergence and impact on bacterial virulence assessed by in vivo studies coupled to functional genomics

The recent discovery of strains resistant to vancomycin, thus far considered as the only uniformly active agent against all staphylococci, is a serious public health issue since it could nearly destroy the therapeutic armentarium against staphylococci. This projet aims to identify genes responsible for resistance to vancomycin.

Background
Staphylococcal infections, in particular those acquired in a hospital setting, are a major public health problem. Many hospital-acquired strains of staphyloccocci are resistant to many and sometimes nearly all commercially available antibiotics. The recent discovery of strains resistant to vancomycin, thus far considered as the only uniformly active agent against all staphylococci, is a serious threat since it could nearly destroy the therapeutic armentarium against staphylococci. Resistance mechanisms to vancomycin as well as teicoplanin, another agent belonging to a family of antibiotics named glycopeptides, are still mysterious. Furthermore, the detection of strains exhibiting resistance to the glycopeptides is quite difficult, since no standard method of clinical microbiology can yield reliable data.

Aim
Identify genes responsible for resistance to the glycopeptides. The discovery of these resistance genes is difficult since they were not acquired from another bacterial species. At the opposite, this resistance may be caused by significant changes in the activity of some of the genes belonging to the staphylococci. In turn, these changes may lead to metabolic changes that may eventually decrease the microbial susceptibility to the glycopeptides. To study these metabolic changes in a global way, we use microarrays allowing to simultaneously recording the activity of all 2800 genes present in staphylococci. These microarrays are highly efficient diagnostic tools, combining the most recent biotechnological, microtechnical, and bioinformatic developments. This technology allows us to currently identify and characterise some of the most important genes contributing to glycopeptide resistance and also provides important information on the way glycopeptide-resistant bacteria may modify their virulence.

Significance
This project will promote the development of rapid and reliable methods for detecting staphylococci resistant to vancomycin or teicoplanin. This will facilitate the screening of resistant bacteria and prevent their spreading to the hospital and the community. This project will also promote the development of novel antimicrobial agents active against the glycopeptide-resistant staphylococci.
Direct link to Lay Summary Last update: 21.02.2013

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