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Shigella-mediated oxygen depletion is essential for intestinal mucosa colonization


Pathogenic enterobacteria face various oxygen (O2) levels during intestinal colonization from the O2-deprived lumen to oxygenated tissues. Using Shigella flexneri as a model, we have previously demonstrated that epithelium invasion is promoted by O2 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 O2 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.

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Fig. 1: Hypoxia is specifically induced by Shigella within foci of infection.
Fig. 2: Neutrophils are not essential for O2 depletion in infected tissues, which is mainly caused by Shigella aerobic respiration.
Fig. 3: Aerobic respiration is required for hypoxia induction and efficient colonic mucosa colonization by Shigella in vivo.
Fig. 4: S. flexneri T3SS is inactive in the colonic mucosa, supporting foci of infection extension.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.


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We acknowledge France-BioImaging infrastructure, supported by the French National Research Agency (ANR-10-INBS-04, Imagopole; to J.-Y.T.), ANR JCJC 2017-17-CE15-0012 (to B.S.M.) and the European Research Council (ERC grant 2009-AdG HOMEOPATH; to P.J.S.). E.T.A. was a Pasteur Foundation and Pasteur-Roux fellow.

Author information




B.S.M., J.-Y.T. and E.T.A. designed the experiments, interpreted the data and wrote the paper. M.A. designed the Shigella mutants. G.N., L.I., A.A., M.F. and F.-X.C.-V. contributed to studying the Shigella mutants in vitro and in vivo. J.-Y.T. conducted quantitative analysis of the data. A.D., S.L.S. and P.J.S. contributed to data interpretation.

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Correspondence to Benoit S. Marteyn.

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Supplementary Figs. 1–5 and Supplementary Tables 1–12.

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Tinevez, JY., Arena, E.T., Anderson, M. et al. Shigella-mediated oxygen depletion is essential for intestinal mucosa colonization. Nat Microbiol 4, 2001–2009 (2019).

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