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Modulation of Shigella virulence in response to available oxygen in vivo


Bacteria coordinate expression of virulence determinants in response to localized microenvironments in their hosts. Here we show that Shigella flexneri, which causes dysentery, encounters varying oxygen concentrations in the gastrointestinal tract, which govern activity of its type three secretion system (T3SS). The T3SS is essential for cell invasion and virulence1. In anaerobic environments (for example, the gastrointestinal tract lumen), Shigella is primed for invasion and expresses extended T3SS needles while reducing Ipa (invasion plasmid antigen) effector secretion. This is mediated by FNR (fumarate and nitrate reduction), a regulator of anaerobic metabolism that represses transcription of spa32 and spa33, virulence genes that regulate secretion through the T3SS. We demonstrate there is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi. This would reverse the anaerobic block of Ipa secretion, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.

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Figure 1: Influence of anaerobiosis and FNR on Shigella invasion.
Figure 2: T3SS structure and function are modified by ambient O2.
Figure 3: Regulation of Shigella virulence genes by O 2 and FNR.
Figure 4: The presence of O 2 encountered by Shigella in vitro and in vivo


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This work was supported by the Fondation pour la Recherche Médicale, the Royal Society, an ERC Advanced Grant (HOMEOEPITH), and the European Union (QLRT-1999-00938). Work in CMT’s laboratory is supported by the Wellcome Trust and The Medical Research Council, and PJS is a Howard Hughes Medical Institute scholar. Imaging was performed at the PFID station (Institut Pasteur). We are grateful to J. Green for the anti-FNR pAbs and advice. R. Exley, D. Holden and K. Ray provided suggestions and reviewed the manuscript; we thank M.-A. Nicola for technical help.

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Authors and Affiliations



B.M., N.P.W. and J.M. performed experiments with Shigella. D.F.B. and J.A.C. provided technical support and advice for electrophoretic mobility shift assays and analysis of the fusions. J.G.S. analysed the lipopolysaccharide, M.-C.P. carried out EM, and F.P. performed the oxygen measurements. C.M.T. and P.S. provided advice and overall direction, and wrote the paper.

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Correspondence to Philippe Sansonetti or Christoph M. Tang.

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The authors declare no competing financial interests.

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Marteyn, B., West, N., Browning, D. et al. Modulation of Shigella virulence in response to available oxygen in vivo. Nature 465, 355–358 (2010).

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