Modulation of Shigella Virulence in Response to Available Oxygen in Vivo

Overview

Journal Nature

Specialty Science

Date 2010 May 4

PMID 20436458

Citations 176

Authors

Benoit Marteyn

Nicholas P West

Douglas F Browning

Jeffery A Cole

Jonathan G Shaw

Fredrik Palm

Joelle Mounier

Marie-Christine Prevost

Philippe Sansonetti

Christoph M Tang

Affiliations

Soon will be listed here.

Abstract

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 virulence. 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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