TROCAR - Translation Research On Combating Antimicrobial Resistance

Summary:

The health care systems of most European countries are based on a continuum from acute care hospitals, through other health care facilities to the community. This framework provides the perfect opportunity for the wide-spread dissemination of high-risk resistant clones or genetic-resistant elements. The driving concept of TROCAR is to investigate the fundamentals of the epidemiology of new highly virulent multiresistant strains of MRSA, VRE, ESMAC-BL-producing Enterobacteriaceae, multidrug-resistant P. aeruginosa and A. baumannii will focus on three major strategic aims: 1. The definition of the major high-risk resistant clones based on an appropriate representative collection and new clinical strains obtained during molecular epidemiological studies, in hospitals and laboratories collaborating with their respective National Excellence Laboratories in European countries using a standardised protocol. 2. The promotion of collaborative European research to investigate, by genomic and proteomic approaches, specific traits associated with virulence, transmission, persistence and resistance of epidemic clones in comparison with non-epidemic clones as well as resistance determinants and their genetic location in horizontal gene transfer units and their genetic environment. 3.The development of bioinformatics tools to fully exploit the genomics data and allow the rapid identification of resistant strains with heightened epidemic potential. By combining the outputs of the project it will be possible to provide tools for monitoring the spread of key community and nosocomial pathogens, to provide the scientific basis for an early warning system when isolates of a particular epidemicity appear in the community and nosocomial settings, to create a knowledge base for combating epidemicity and virulence, to characterise specific genetic elements carrying genes encoding ESCMAC-BL, to identify potential reservoirs of antibiotic resistance genes amongst community and nosocomial pathogens involving multi-drug resistance and to establish the bioinformatic tools and infrastructure necessary to achieve the ultimate TROCAR goal: “to recommend novel control measures to limit or prevent the spread of highly virulent multi-drug resistant clones: from molecule to preventive action”.

Problem:

The health care systems of most European countries are based on a continuum from acute care hospitals, though other health care facilities to the community. This framework provides the perfect opportunity for the wide-spread dissemination of high-risk resistant clones or genetic-resistant elements. High-risk resistant clones are bacterial clones that associate: 1) mechanisms of resistance to antibiotics of critical clinical importance and 2a) the ability to be transmitted with high efficiency among hospitalised patients or 2b) with particular ability to produce severe or invasive infections; or 2c) the ability to efficiently colonize human hosts during long periods of time. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), Extended-spectrum, metallo- and acquired AmpC beta-lactamase producing Enterobacteriaceae (ESMAC-BL), multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii are the paradigm of resistant bacteria with a great potential for spread.

In addition, selection, dissemination and evolution of antibiotic-resistant genes and their genetic environmental location have been less studied and are essential to better design overall control strategies. The selection of the most appropriate strategies to control the dissemination of these microorganisms is under debate largely because of the lack of a definition of the specific traits of the epidemic strains.

This proposal is therefore motivated by three main questions:

1. Are certain resistant strains more epidemic than others? Are certain strains more prone to persist in the human environment? If so, why?
2. Do epidemic and persistent strains have specific virulence, physiological, colonization, or transmission-facilitating traits that non-epidemic strains do not have?
3. What is the origin and mechanisms of acquisition of these fitness-increasing traits in resistant bacteria? Might the elucidation of these mechanism provide new insights for prediction and intervention?

TROCAR will harness the collective potential of several leading European research groups for advanced molecular investigations into the natural history and evolutionary trails of new and highly virulent multi-drug resistant strains of bacterial pathogens, causing particular concern to hospitals and the community, and will provide the scientific and public health community in Europe with advanced state-of-the-art research lines, for interventions and progress towards goals for the strategic control of these pathogens.

The driving concept of this project is to investigate the fundamentals of the epidemiology of new highly virulent multiresistant strains of MRSA, VRE, ESMAC-BL-producing Enterobacteriaceae, multidrug-resistant P. aeruginosa and A. baumannii and will focus on three major strategic aims (Flow-chart – Figure 1):

1. The definition of the major high-risk resistant clones based on an appropriate representative collection and new clinical strains obtained during molecular epidemiological studies, in hospitals and laboratories collaborating with their respective National Excellence Laboratories in European countries using a standardised protocol.
2. The promotion of collaborative European research to investigate, by genomic and proteomic approaches, specific traits associated with virulence, transmission, persistence and resistance of epidemic clones in comparison with non-epidemic clones as well as resistance determinants and their genetic location in horizontal gene transfer units and their genetic environment.
3. The development of bioinformatic tools to fully exploit the genomics data and allow the rapid identification of resistant strains with heightened epidemic potential.

Coordinator:

Partners: