title: MxiC is secreted by and controls the substrate specificity of the Shigella flexneri type III secretion apparatus.
abstract: 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.
authors.affiliation: Laboratoire de Bactériologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Route de Lennik, 808, CP: 614b, 1070, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Botteaux
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Sory
authors.forename: Latéfa
authors.initials: L
authors.lastname: Biskri
authors.forename: Claude
authors.initials: C
authors.lastname: Parsot
authors.forename: Abdelmounaaïm
authors.initials: A
authors.lastname: Allaoui
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D016296:Mutagenesis; D021381:Protein Transport; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C079724:MxiE protein, Shigella flexneri; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C478167:Spa47 protein, Shigella flexneri