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|Título:||The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages|
Ramiro, Ricardo S.
de Sousa, Jorge A. Moura
Soares, Miguel P.
|Citação:||Miskinyte M, Sousa A, Ramiro RS, de Sousa JAM, Kotlinowski J, et al. (2013) The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages. PLoS Pathog 9(12): e1003802. doi:10.1371/journal.ppat.1003802|
|Resumo:||Antagonistic interactions are likely important driving forces of the evolutionary process underlying bacterial genome complexity and diversity. We hypothesized that the ability of evolved bacteria to escape specific components of host innate immunity, such as phagocytosis and killing by macrophages (MΦ), is a critical trait relevant in the acquisition of bacterial virulence. Here, we used a combination of experimental evolution, phenotypic characterization, genome sequencing and mathematical modeling to address how fast, and through how many adaptive steps, a commensal Escherichia coli (E. coli) acquire this virulence trait. We show that when maintained in vitro under the selective pressure of host MΦ commensal E. coli can evolve, in less than 500 generations, virulent clones that escape phagocytosis and MΦ killing in vitro, while increasing their pathogenicity in vivo, as assessed in mice. This pathoadaptive process is driven by a mechanism involving the insertion of a single transposable element into the promoter region of the E. coli yrfF gene. Moreover, transposition of the IS186 element into the promoter of Lon gene, encoding an ATP-dependent serine protease, is likely to accelerate this pathoadaptive process. Competition between clones carrying distinct beneficial mutations dominates the dynamics of the pathoadaptive process, as suggested from a mathematical model, which reproduces the observed experimental dynamics of E. coli evolution towards virulence. In conclusion, we reveal a molecular mechanism explaining how a specific component of host innate immunity can modulate microbial evolution towards pathogenicity.|
|Versão do Editor:||http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003802|
|Aparece nas colecções:||EB - Artigos|
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|journal.ppat.1003802 (1).pdf||artigo principal||1,8 MB||Adobe PDF||Ver/Abrir|
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