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Modulation of Shigella virulence in response to available oxygen in vivo

机译：体内对可用氧的反应对志贺氏菌毒力的调节

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摘要

Bacteria coordinate expression of virulence determinants in res-ponse 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.
机译：细菌协调毒力决定簇的表达，以响应宿主中的局部微环境。在这里，我们显示了引起痢疾的弗氏志贺氏菌在胃肠道中遇到了不同的氧气浓度，这些氧气浓度控制着它的三型分泌系统（T3SS）的活性。 T3SS对于细胞侵袭和毒性至关重要。在厌氧环境中（例如胃肠道内腔），志贺氏菌可引发侵染并表达延长的T3SS针，同时减少Ipa（侵袭质粒抗原）效应子的分泌。这是由FNR（富马酸盐和硝酸盐还原）介导的，FNR是一种厌氧代谢的调节剂，可抑制spa32和spa33的转录，spa32和spa33是通过T3SS调节分泌的毒力基因。我们证明胃肠道粘膜附近有一个相对氧合作用的区域，这是由绒毛尖端毛细血管网络的扩散引起的。这将逆转Ipa分泌的厌氧性阻滞，从而使T3SS在其确切的作用部位活化，从而增强入侵和毒力。

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  • 来源
    《Nature》 |2010年第7296期|p.355-358|共4页
  • 作者

    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;

  • 作者单位

    Centre for Molecular Microbiology and Infection, Department of Microbiology, Flowers Building, Imperial College London, London SW7 2AZ, UK;

    Centre for Molecular Microbiology and Infection, Department of Microbiology, Flowers Building, Imperial College London, London SW7 2AZ, UK Centenary Institute, Newtown, New South Wales 2042, Australia;

    School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK;

    School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK;

    Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK;

    Department of Medical Cell Biology, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden;

    Unite de Pathogenie Microbienne Moleculaire, and Unite INSERM786, Institut Pasteur, 28 rue du Dr Roux, F-75724 Paris Cedex 15, France;

    Plateforme de Microscopie electronique, Institut Pasteur, 25 Rue du Docteur Roux, F-75724 Paris cedex 15, France;

    Unite de Pathogenie Microbienne Moleculaire, and Unite INSERM786, Institut Pasteur, 28 rue du Dr Roux, F-75724 Paris Cedex 15, France College de France, 11 Place Marcelin Berthelot, F-75231, Paris Cedex 05, France;

    Centre for Molecular Microbiology and Infection, Department of Microbiology, Flowers Building, Imperial College London, London SW7 2AZ, UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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