Interplay between predicted inner-rod and gatekeeper in controlling substrate specificity of the type III secretion system

Youness Cherradi, Lionel Schiavolin, Simon Moussa, Alaeddine Meghraoui, Ahmed Meksem, Latéfa Biskri, Mohamed Azarkan, Abdelmounaaïm Allaoui, Anne Botteaux

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The type III secretion apparatus (T3SA) is a multi-protein complex central to the virulence of many Gram-negative pathogens. Currently, the mechanisms controlling the hierarchical addressing of needle subunits, translocators and effectors to the T3SA are still poorly understood. In Shigella, MxiC is known to sequester effectors within the cytoplasm prior to receiving the activation signal from the needle. However, molecules involved in linking the needle and MxiC are unknown. Here, we demonstrate a molecular interaction between MxiC and the predicted inner-rod component MxiI suggesting that this complex plugs the T3SA entry gate. Our results suggest that MxiI-MxiC complex dissociation facilitates the switch in secretion from translocators to effectors. We identified MxiCF206S variant, unable to interact with MxiI, which exhibits a constitutive secretion phenotype although it remains responsive to induction. Moreover, we identified the mxiIQ67A mutant that only secretes translocators, a phenotype that was suppressed by coexpression of the MxiCF206S variant. We demonstrated the interaction between MxiI and MxiC homologues in Yersinia and Salmonella. Lastly, we identified an interaction between MxiC and chaperone IpgC which contributes to understanding how translocators secretion is regulated. In summary, this study suggests the existence of a widely conserved T3S mechanism that regulates effectors secretion.

langue originaleAnglais
Pages (de - à)1183-1199
Nombre de pages17
journalMolecular Microbiology
Numéro de publication6
Les DOIs
Etat de la publicationPublié - mars 2013

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