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Translational Research on Combating Antimicrobial Resistance

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Europe fights anti-microbial resistance

Drug resistance is a significant health threat today and is exacerbated by the injudicious use of antibiotics. An early warning system is necessary to identify and prevent the spread of epidemic strains.

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High-risk drug-resistant bacteria are of critical clinical importance that can be transmitted with high efficiency among hospitalised patients. Equally dangerous are the clones that cause significant infections for long periods of time. Among the species with a great potential for spread is methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), AmpC beta-lactamase producing Enterobacteriaceae (ESMAC-BL) as well as multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. The EU-funded TROCAR (Translational research on combating antimicrobial resistance) project worked on determining the natural history and evolutionary trajectories of highly virulent drug-resistant strains of bacterial pathogens. The activities were designed to provide the scientific and public health authorities with research lines for testing new interventions against these pathogens. Using epidemiological data as well as genomic and proteomic approaches, researchers were able to define specific traits associated with virulence, transmission, and persistence of resistant clones. Direct comparison with non-epidemic clones allowed them to identify resistance determinants and their genetic localisation. For example, in VRE, a global transcriptomic approach identified AsrR as a key regulator modulating opportunistic traits and pathogenesis. Collectively, the generated information was employed to produce an inventory of strains for MRSA, VRE, ESMAC-BL and Pseudomonas. The geographical distribution of MRSA clones has been displayed on a web-based mapping tool using a Google interface. In addition, the consortium developed new array-based tools for the rapid and simple detection of resistance genes in circulating ESMAC-BL. One of the key mechanisms for the acquisition of resistance is the horizontal transfer of DNA between bacteria. The TROCAR work revealed significant variation in recombination rates between different phylogenetic groups, illustrating interplay between epidemiological factors and molecular dynamics. Taken together, the TROCAR observations and tools will help identify potential reservoirs of antibiotic resistance genes and monitor the spread of key community and nosocomial pathogens.

Keywords

Antibiotic resistance, MRSA, VRE, phylogenetic, epidemiology

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