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Vaccine-development to combat the emergence of vancomycin-resistant Enterococcus faecium

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Vancomycin-Resistant Enterococcus faecium (VREF) are important emerging antibiotic resistant pathogens, causing infections predominantly in severely ill and immunocompromised patients. VREF are resistant to almost all available antibiotics and its epidemiology in the recent decade represents the worst-case scenario of emergence of antibiotic resistance: From a nearly non-existing nosocomial pathogen in 1990 to a feared pathogen in 2000. As new classes of antibiotics are unlikely to be developed in the near future new modalities to control spread and prevent infections with multiple antibiotic-resistant microorganisms are needed. VREF are present in different host populations, such as livestock, household animals, healthy European subjects and hospitalised patients worldwide. Molecular studies have identified a genetic lineage of VREF associated with hospital outbreaks and clinical infections in 3 continents (Europe, North-America and Australia). This so-called "epidemic" genetic lineage is characterised by ampicillin-resistance and a virulence factor, the enterococcal surface protein (Esp). Esp is part of a pathogenicity island (PAI), which probably contains more virulence factors. Although the exact role of Esp in the pathogenesis of E. faecium infections is not fully understood, it has been demonstrated that homologous of this polypeptide like Esp of E. faecalis, Rib and C-Alpha of Group B streptococci and R28 of group A streptococci are involved in virulence and are able to confer protective immunity. The aim of this project is to assess whether human immune globulins directed against cell wall proteins of VREF (like Esp and other virulence factors) can be used as prophylaxis to prevent infections and enteric colonization. In addition, cell wall proteins of VREF will be used to develop sub-unit vaccines to prevent infections and to develop recombinant live-vaccines to prevent colonization. The development of passive and active immunization strategies based on newly identified virulence factors offers unique possibilities for new preventive options to combat the emergence of multiple antibiotic-resistant pathogens.

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Projectnummer:
61000008
Looptijd: 100%
Looptijd: 100 %
2005
2009
Onderdeel van programma:
Projectleider en penvoerder:
Dr. R.J.L. Willems
Verantwoordelijke organisatie:
Universitair Medisch Centrum Utrecht