Evolution of plasmid-mediated resistance in Pseudo.. (PLASREVO)
Evolution of plasmid-mediated resistance in Pseudomonas aeruginosa
Date du début: 1 oct. 2012,
Date de fin: 30 sept. 2014
"Antimicrobial resistance in bacteria is currently one of the most concerning threats for public health. Up to 400,000 patients suffer from infections resistant to multiple antibiotics in Europe annually, giving rise to more than 18,000 deaths every year. Hence, a better control of the rise and spread of antimicrobial resistance in pathogenic bacteria is crucial to improve the health of European citizens. Bacteria acquire resistance to antibiotics through two principal routes, (i) chromosomal mutations and (ii) plasmid acquisition. Plasmids are extrachromosomal DNA elements responsible for the spread of antimicrobial resistance determinants among bacteria, as they can disseminate by horizontal gene transfer (conjugation and/or transformation).Previous works have shown that aspects as the mechanistic basis of drug resistance and the antibiotic treatment regimes are crucial for understanding the evolution of population genetics of chromosomal-mediated resistance. Here, we would like to determine the key population genetic parameters that influence the rising and the spread of plasmid-mediated resistance. Specifically, we will determine for both (a) plasmid and (b) chromosomal-mediated resistance:(i) The rate of acquisition of resistance.(ii) The fitness costs and benefits of resistance.(iii) The potential for compensatory adaptation to ameliorate the cost of resistance.We will quantify these parameters using in vivo and in vitro experimental evolution experiments with the pathogenic bacterium Pseudomonas aeruginosa.This work will help us to understand and prevent the concerning phenomenon of antimicrobial resistance spread among pathogenic bacteria, and will provide information of biological and clinical relevance to make predictions about how innovative therapeutic approaches could impact plasmid-mediated resistance dynamics."
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