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Characterization of the role of lpaA on the cytoskeletal anchorage of Shigella flexneri

Abstract : Shigella invades cells of the intestinal epithelium by injecting effector proteins through a Type III Secretion System (T3SS). The type III effector IpaA binds to talin and vinculin through three Vinculin Binding Sites (VBSs), promoting cytoskeletal anchorage to promote bacterial internalization. As opposed to other invasive bacteria, Shigella does not show constitutive cell binding activity but triggers transient adhesion through T3SS activation. IpaA VBS3 was found to be structurally analogous to talin H5 helix, which, together with H1-H4, forms the R1 talin bundle. Functional analysis identified IpaA VBS3 is necessary for talin recruitment to Shigella entry foci and formation of nascent adhesions and filopodia. IpaA VBS3 also stimulates filopodial capture of bacteria and stabilizes cell adhesions in invaded cells. On the other hand, structural models of IpaA VBSs/Vinculin interactions indicate a novel mode of vinculin activation, involving conformational changes in vinculin head domain that leads to trimerization and stabilization of focal adhesions. IpaA was also observed to be injected by "kissing-and-running" bacteria, facilitating additional bacterial binding and invasion events. This IpaA-dependent priming was dependent on IpaA VBS3 but not on IpaA VBS1-2. Injected IpaA was observed to form clusters apposed to the cell apical side and to induce integrin clustering. Overall, the results indicate that IpaA triggers general changes in cell adhesive properties and promotes a cooperative mechanism of Shigella invasion.
Keywords : IpaA
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Submitted on : Monday, February 1, 2021 - 1:43:25 PM
Last modification on : Thursday, March 24, 2022 - 10:43:58 AM
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  • HAL Id : tel-03127237, version 1


Daniel-Isui Aguilar-Salvador. Characterization of the role of lpaA on the cytoskeletal anchorage of Shigella flexneri. Microbiology and Parasitology. Université Paris Cité, 2019. English. ⟨NNT : 2019UNIP7144⟩. ⟨tel-03127237⟩



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