ACE - Approaches to Control multi-resistant Enterococci: Studies on molecular ecology, horizontal gene transfer, fitness and prevention. (Life sciences, genomics and biotechnology for health) (2007-02-01 - 2010-01-31) (»add to infobox)

Vancomycin-reistant enterococci (VRE) have become the paradigm of the post-antibiotic era. Nosocomial VRE-infections are rising in all European countries, with proportions >10% among enterococcal bloodstream infections in 5 countries in 2004. From a microbial perspective, emergence of VRE represents a dual-edged sword: they are amongst the most resistant opportunistic nosocomial pathogens with an increasing impact on patients' health care. Moreover, and maybe even more important, their unprecedented capacity of genetic exchange make them perfect hubs for resistance genes facilitating horizontal gene transfer amongst bacterial species. Genetic population analyses of Enterococcus faecium revealed the presence of a High-Risk Enterococcal Clonal Complex (HiRECC) resistant to multiple antibiotics and responsible for the vast majority of nosocomial VRE infections and hospital outbreaks worldwide. In this proposal, the evolutionary development of HiRECC in E. faecium and E. faecalis will be further unraveled and combined with new knowledge on intra- and inter-species gene transfer (including antibiotic resistance genes) and biological fitness costs of hospital adaptation. This will improve our understanding on the ecological abundance of HiRECC in hospitals. Based on this we will develop novel strategies to control spread of HiRECC through modulation of gut colonization by 1) probiotics, specifically selected to out compete HiRECC and 2) vaccination with Lactococcus lactis particles carrying HiRECC specific antigens. In addition, a novel therapeutic approach will be explored by identifying targets of HiRECC for passive immunization with human monoclonal antibodies. In contrast to MRSA, widespread nosocomial endemicity of VRE has not yet been established in European hospitals and, therefore, immediate development of alternatives for increasingly ineffective antibiotics is needed, both for patient treatment as well as to control further spread of antibiotic resistance.'

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