MxiC is secreted by and controls the substrate specificity of the Shigella flexneri type III secretion apparatus

Authors

  • Anne Botteaux,

    1. Laboratoire de Bactériologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Route de Lennik, 808, CP: 614b, 1070, Brussels, Belgium.
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  • Marie Paule Sory,

    1. Laboratoire de Bactériologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Route de Lennik, 808, CP: 614b, 1070, Brussels, Belgium.
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    • Present address: Rue du Veneur, 67, 7850, Enghien, Belgium.

  • Latéfa Biskri,

    1. Laboratoire de Bactériologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Route de Lennik, 808, CP: 614b, 1070, Brussels, Belgium.
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  • Claude Parsot,

    1. Laboratoire de Pathogénie Microbienne: Institut Pasteur, 27-28 Rue du Dr Roux, 75725, Paris Cedex 15, France.
    2. INSERM U786, 25 rue du Dr Roux, F-75724 Paris Cedex 15, France.
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  • Abdelmounaaïm Allaoui

    Corresponding author
    1. Laboratoire de Bactériologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Route de Lennik, 808, CP: 614b, 1070, Brussels, Belgium.
      *E-mail aallaoui@ulb.ac.be; Tel. (+32) 2 555 62 51; Fax (+32) 2 555 61 16.
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*E-mail aallaoui@ulb.ac.be; Tel. (+32) 2 555 62 51; Fax (+32) 2 555 61 16.

Summary

Many Gram-negative pathogenic bacteria use a type III secretion (T3S) system to interact with cells of their hosts. Mechanisms controlling the hierarchical addressing of needle subunits, translocators and effectors to the T3S apparatus (T3SA) are still poorly understood. We investigated the function of MxiC, the member of the YopN/InvE/SepL family in the Shigella flexneri T3S system. Inactivation of mxiC led specifically to a deregulated secretion of effectors (including IpaA, IpgD, IcsB, IpgB2, OspD1 and IpaHs), but not of translocators (IpaB and IpaC) and proteins controlling the T3SA structure or activity (Spa32 and IpaD). Expression of effector-encoding genes controlled by the activity of the T3SA and the transcription activator MxiE was increased in the mxiC mutant, as a consequence of the increased secretion of the MxiE anti-activator OspD1. MxiC is a T3SA substrate and its ability to be secreted is required for its function. By using co-purification assays, we found that MxiC can associate with the Spa47 ATPase, which suggests that MxiC might prevent secretion of effectors by blocking the T3SA from the inside. Although with a 10-fold reduced efficiency compared with the wild-type strain, the mxiC mutant was still able to enter epithelial cells.

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