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Rôle de l’îlot génomique pks dans la synthèse des sidérophores-microcines chez Escherichia coli

Olivia Vong 247 Comments 0 likes
Image par Gerd Altmann de Pixabay

Directeur de thèse : Eric Oswald

Rôle de l’îlot génomique pks dans la synthèse des sidérophores-microcines chez Escherichia coli 

Les sidérophores-microcines H47 et M (MccH47 et MccM) sont des peptides antimicrobiens hybrides, constitués d’une entité peptidique couplée à un groupement dérivé d’un sidérophore, l’entérobactine. Elles sont à l’origine de l’activité antagoniste de la souche Escherichia coli Nissle (EcN) vis-à-vis d’entérobactéries pathogènes. Cette souche est également porteuse de l’îlot pks à l’origine de la synthèse d’une génotoxine, la colibactine. Nous avons déterminé que la peptidase ClbP codée par l’îlot pks était indispensable à la synthèse des sidérophores-microcines chez EcN. C’est la partie C-terminale ancrant ClbP dans la membrane interne qui permet la synthèse des MccH47 et MccM, et non son site catalytique essentiel à la maturation de la colibactine. Par rapport au système génétique conduisant à la synthèse des MccH47 et MccM chez les souches E. coli CA46 et CA58, l’îlot sidérophores-microcines de EcN est tronqué. Nous avons montré que IroB, impliqué dans la synthèse des salmochélines était indispensable à l’activité antagoniste de EcN, probablement en assurant le rôle de son homologue McmL manquant chez EcN. Nous avons déterminé que l’ensemble des souches séquencées de E.coli portant un îlot microcines tronqué possédait les îlots pks et salmochélines, ce qui renforce l’hypothèse d’une interdépendance et d’une coévolution de ces systèmes. Nous avons étudié la présence des îlots microcines, pks et salmochélines dans une collection de souches de E. coli responsables de pyélonéphrites, cystites ou bactériuries asymptomatiques. L’analyse génétique de plus de 200 souches recueillies à la suite d’examens cytobactériologiques des urines a permis de confirmer l’association systématique de ces 3 îlots. La proportion des souches productrices de MccH47 et MccM est identique quel que soit le tableau clinique, ce qui tendrait à prouver qu’il s’agit davantage d’un facteur permettant la colonisation de l’arbre urinaire à partir de la niche intestinale plutôt que d’un facteur de virulence dans le tractus urinaire.

Clémence Massip
MASSIP.C@chu-toulouse.fr

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