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Intégrons de multirésistance : coût biologique et dynamique d' évolution du promoteur des cassettes

Abstract : Resistance integrons are genetic platforms able to catch and express resistance genes embedded within gene cassettes. Capture and reshuffling of gene cassettes are mediated by the integrase whose expression is regulated by the SOS response in E. coli. Gene cassettes are then expressed from the Pc promoter.This work aims to clarify the evolution dynamic of integrons.In a first part, the fitness cost of class 1 integron was assessed in E. coli. Results reveal that integrons are low cost structures and that their cost is reduced by the SOS-mediated repression system. While repressed, the cost of an integron mostly depends on cassettes array expression. The cost of an integron therefore increases with Pc strength and the number of cassettes in the array. Furthermore, different cassettes exhibit different costs.In a second part, the evolution dynamic of Pc promoter was assessed in response to antibiotic pressures. An E. coli strain, carrying a plasmidic integron with a weak Pc promoter, was propagated in chemostat for 200 generations. The deep-sequencing of evolved populations did not reveal any mutations in the promoter region. On the other hand, evolved bacteria presented evidence of chromosomal adaptation. In these conditions, the lack of evolution within the Pc region could reveal either a biological reality or an experimental protocol to optimize.
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Yohann Lacotte. Intégrons de multirésistance : coût biologique et dynamique d' évolution du promoteur des cassettes. Médecine humaine et pathologie. Université de Limoges, 2016. Français. ⟨NNT : 2016LIMO0068⟩. ⟨tel-01657881⟩

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