BIOCHARGE

Investigation into the Biological Cost and Adaptation of the Host to Antibiotic Resistance on mobile Genetic Elements in Enterococcus species

Coordinatore	UNIVERSITY COLLEGE LONDON    more  Organization address address: GOWER STREET city: LONDON postcode: WC1E 6BT contact info Titolo: Ms. Nome: Greta Cognome: Borg-Carbott Email: send email Telefono: 442031000000 Fax: 442078000000
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	210˙092 €
EC contributo	210˙092 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-IEF
Funding Scheme	MC-IEF
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-06-06   -   2014-06-05

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY COLLEGE LONDON  Organization address address: GOWER STREET city: LONDON postcode: WC1E 6BT contact info Titolo: Ms. Nome: Greta Cognome: Borg-Carbott Email: send email Telefono: 442031000000 Fax: 442078000000	UK (LONDON)	coordinator	210˙092.80

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 Obiettivo del progetto (Objective)

'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.'

Introduzione (Teaser)

Antibiotic resistance in bacteria is one of the greatest challenges to modern medicine. An EU project has investigated the effects of carrying resistance genes on the bacteria themselves and its significance for antimicrobial resistance management.