Iron Homeostasis Regulates the Genotoxicity of Escherichia coli That Produces Colibactin.
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.
IRSD, Université de Toulouse, INSERM, INRA, ENVT, Toulouse, France.|Université Toulouse III Paul Sabatier, Toulouse, France.
Sophie
S
Tronnet
IRSD, Université de Toulouse, INSERM, INRA, ENVT, Toulouse, France.|Université Toulouse III Paul Sabatier, Toulouse, France.|CHU Toulouse, Service de Bactériologie-Hygiène, Toulouse, France.
Christophe
C
Garcie
Institute of Hygiene, University of Münster, Münster, Germany.|Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany.
Nadine
N
Rehm
Institute of Hygiene, University of Münster, Münster, Germany.|Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany.
Ulrich
http://orcid.org/0000-0001-9949-1898
U
Dobrindt
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.
Eric
E
Oswald
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.
Patricia
P
Martin
D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D004926:Escherichia coli / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006706:Homeostasis / Q000502:physiology*; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism*; D012329:RNA, Bacterial
D001426:Bacterial Proteins; D010455:Peptides; D061065:Polyketides; D012329:RNA, Bacterial; C569566:colibactin; D007501:Iron