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- Marteyn, Benoit, et al.
(author)
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Modulation of Shigella virulence in response to available oxygen in vivo
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 465:7296, s. 355-358
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Journal article (peer-reviewed)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(1). 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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| 2. |
- Paz, Irit, et al.
(author)
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Galectin-3, a marker for vacuole lysis by invasive pathogens
- 2010
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In: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 12:4, s. 530-544
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Journal article (peer-reviewed)abstract
- P>Shigella bacteria invade macrophages and epithelial cells and following internalization lyse the phagosome and escape to the cytoplasm. Galectin-3, an abundant protein in macrophages and epithelial cells, belongs to a family of beta-galactoside-binding proteins, the galectins, with many proposed functions in immune response, development, differentiation, cancer and infection. Galectins are synthesized as cytosolic proteins and following non-classical secretion bind extracellular beta-galactosides. Here we analysed the localization of galectin-3 following entry of Shigella into the cytosol and detected a striking phenomenon. Very shortly after bacterial invasion, intracellular galectin-3 accumulated in structures in vicinity to internalized bacteria. By using immuno-electron microscopy analysis we identified galectin-3 in membranes localized in the phagosome and in tubules and vesicles that derive from the endocytic pathway. We also demonstrated that the binding of galectin-3 to host N-acetyllactosamine-containing glycans, was required for forming the structures. Accumulation of the structures was a type three secretion system-dependent process. More specifically, existence of structures was strictly dependent upon lysis of the phagocytic vacuole and could be shown also by Gram-positive Listeria and Salmonella sifA mutant. We suggest that galectin-3-containing structures may serve as a potential novel tool to spot vacuole lysis.
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