Open AccessShigella-mediated oxygen depletion is essential for intestinal mucosa colonization
Author(s) -
Jean-Yves Tinévez,
Ellen T. Arena,
Mark Anderson,
Giulia Nigro,
Louise Injarabian,
Antonin C André,
Mariana L. Ferrari,
François-Xavier Campbell-Valois,
Anne Devin,
Spencer Shorte,
Philippe Sansonetti,
Benoît Marteyn
Publication year - 2019
Publication title -
nature microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.305
H-Index - 79
ISSN - 2058-5276
DOI - 10.1038/s41564-019-0525-3
Subject(s) - shigella flexneri , microbiology and biotechnology , secretion , biology , intestinal mucosa , pathogen , colonization , oxygenation , epithelium , shigella , type three secretion system , bacteria , virulence , salmonella , escherichia coli , medicine , biochemistry , ecology , gene , genetics
Pathogenic enterobacteria face various oxygen (O 2 ) levels during intestinal colonization from the O 2 -deprived lumen to oxygenated tissues. Using Shigella flexneri as a model, we have previously demonstrated that epithelium invasion is promoted by O 2 in a type III secretion system-dependent manner. However, subsequent pathogen adaptation to tissue oxygenation modulation remained unknown. Assessing single-cell distribution, together with tissue oxygenation, we demonstrate here that the colonic mucosa O 2 is actively depleted by S. flexneri aerobic respiration-and not host neutrophils-during infection, leading to the formation of hypoxic foci of infection. This process is promoted by type III secretion system inactivation in infected tissues, favouring colonizers over explorers. We identify the molecular mechanisms supporting infectious hypoxia induction, and demonstrate here how enteropathogens optimize their colonization capacity in relation to their ability to manipulate tissue oxygenation during infection.