cover image: Oxygen concentration modulates colibactin production

20.500.12592/1gb1ufk

Oxygen concentration modulates colibactin production

31 Dec 2023

Up to 25% of the E. coli strains isolated from the feces of healthy humans harbor the pks genomic island encoding the synthesis of colibactin, a genotoxic metabolite. Evidence is accumulating for an etiologic role of colibactin in colorectal cancer. Little is known about the conditions of expression of colibactin in the gut. The intestine is characterized by a unique oxygenation profile, with a steep gradient between the physiological hypoxic epithelial surface and the anaerobic lumen, which favors the dominance of obligate anaerobes. Here, we report that colibactin production is maximal under anoxic conditions and decreases with increased oxygen concentration. We show that the aerobic respiration control (ArcA) positively regulates colibactin production and genotoxicity of pks+ E. coli in response to oxygen availability. Thus, colibactin synthesis is inhibited by oxygen, indicating that the pks biosynthetic pathway is adapted to the anoxic intestinal lumen and to the hypoxic infected or tumor tissue.

Authors

Nadège Bossuet, Cécile Guyonnet, Camille Chagneau, Min Tang-Fichaux, Marie Penary, Dorian Loubet, Priscilla Branchu, Eric Oswald, Jean-Philippe Nougayrede

Bibliographic Reference
Nadège Bossuet, Cécile Guyonnet, Camille Chagneau, Min Tang-Fichaux, Marie Penary, et al.. Oxygen concentration modulates colibactin production. Gut microbes, 2023, 15 (1), pp.2222437. ⟨10.1080/19490976.2023.2222437⟩. ⟨hal-04147154⟩
DOI
https://doi.org/10.1080/19490976.2023.2222437
HAL Collection
['INSERM - Institut national de la santé et de la recherche médicale', 'Université Paul Sabatier - Toulouse III', 'Archive ouverte en agrobiosciences', 'Institut National de Recherche en Agriculture, Alimentation et Environnement', 'Institut de recherche en santé digestive', 'INRAE Occitanie Toulouse', 'MICA-Unités', 'Toulouse - INP', 'Université Toulouse 3', 'Université Toulouse III / Toulouse INP', 'Ecole Nationale Vétérinaire de Toulouse']
HAL Identifier
4147158
Institution
['Université Toulouse III - Paul Sabatier', 'Institut National Polytechnique (Toulouse)', 'Institut National de la Santé et de la Recherche Médicale', 'Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement', 'Centre Hospitalier Universitaire de Toulouse']
Laboratory
Institut de Recherche en Santé Digestive
Published in
France

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