Iron Homeostasis Regulates the Genotoxicity of Escherichia coli That Produces Colibactin.

Autor:	Tronnet S; IRSD, Université de Toulouse, INSERM, INRA, ENVT, Toulouse, France.; Université Toulouse III Paul Sabatier, Toulouse, France., Garcie C; IRSD, Université de Toulouse, INSERM, INRA, ENVT, Toulouse, France.; Université Toulouse III Paul Sabatier, Toulouse, France.; CHU Toulouse, Service de Bactériologie-Hygiène, Toulouse, France., Rehm N; Institute of Hygiene, University of Münster, Münster, Germany.; Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany., Dobrindt U; Institute of Hygiene, University of Münster, Münster, Germany.; Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany., Oswald E; IRSD, Université de Toulouse, INSERM, INRA, ENVT, Toulouse, France eric.oswald@inserm.fr patricia.martin@inserm.fr.; Université Toulouse III Paul Sabatier, Toulouse, France.; CHU Toulouse, Service de Bactériologie-Hygiène, Toulouse, France., Martin P; IRSD, Université de Toulouse, INSERM, INRA, ENVT, Toulouse, France eric.oswald@inserm.fr patricia.martin@inserm.fr.; Université Toulouse III Paul Sabatier, Toulouse, France.; CHU Toulouse, Service de Bactériologie-Hygiène, Toulouse, France.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2016 Nov 18; Vol. 84 (12), pp. 3358-3368. Date of Electronic Publication: 2016 Nov 18 (Print Publication: 2016).
DOI:	10.1128/IAI.00659-16
Abstrakt:	The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic enterobacteria. Its biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase (PPTase) ClbA. We previously showed that ClbA can also contribute to the production of siderophores. Because the biosynthesis of siderophores is regulated by iron availability, we hypothesized that iron could also modulate the production of colibactin through the transcriptional regulation of clbA This study revealed an increased transcription of clbA under iron-limiting conditions and a decrease of clbA expression in iron-rich media. We demonstrate that clbA transcription is regulated by both the ferric uptake regulator (Fur) and the small regulatory noncoding RNA RyhB. We evidenced that the regulation of the transcription of clbA by Fur and RyhB leads to the regulation of colibactin production. This work highlights the complex mechanism of regulation of an important virulence factor by the two major regulators of bacterial iron homeostasis, making iron a key environmental factor contributing to bacterial virulence and carcinogenesis. (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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