Objetivo
Conjugative transposons (cTns) are mobile genetic elements that mediate the transfer of antibiotic resistance to a wide range of bacteria including enterococci. Preliminary data revealed that the cTns, Tn6000, confer negligible burden or biological cost on enterococcal hosts. Our hypothesis is therefore: cTns have evolved regulatory mechanisms that can minimize their transcription. This leads to minimal biological cost to the host cell and stability of the mobile element within the population, explaining why they persist in bacteria from environments without selective pressure. In addition, we hypothesize that when two or more elements are in the same cell they may recombine to form a single element, again reducing their biological cost and ensuring their propagation. The aims of the project are: to determine if the cTns isolated from E. faecalis affect the fitness of their host and to test the hypothesis that the transcriptional regulation of these mobile elements determines their stability and persistence. Additionally, to determine if different elements can recombine in vivo, potentially forming new, more fit mobile elements and contributing to the evolution of antibiotic resistance development in pathogens. Experimental approach: The stability of the cTns and their recombination potential in enterococci will be assessed in the presence and absence of selective pressure (antibiotics). The absolute and relative fitness of the cTn containing strains will be evaluated and any compensatory mutations in the host will be determined by high throughput sequencing technologies and whole transcriptome shotgun sequencing. Mutagenesis of the regulatory region within the cTns will be carried out to understand the impact on stability of the element and fitness upon the host and to determine if this influences intracellular recombination and the evolution of the mobile elements.
Ámbito científico
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Tema(s)
Convocatoria de propuestas
FP7-PEOPLE-2010-IEF
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Régimen de financiación
MC-IEF - Intra-European Fellowships (IEF)Coordinador
WC1E 6BT LONDON