title: Interplay between predicted inner-rod and gatekeeper in controlling substrate specificity of the type III secretion system.
abstract: 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 MxiC(F)(206)(S) variant, unable to interact with MxiI, which exhibits a constitutive secretion phenotype although it remains responsive to induction. Moreover, we identified the mxiI(Q67A) mutant that only secretes translocators, a phenotype that was suppressed by coexpression of the MxiC(F)(206)(S) 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.
authors: Laboratoire de Bactériologie Moléculaire, Université Libre de Bruxelles, Route de Lennik, 808, 1070, Bruxelles, Belgium.
authors: Youness
authors: Y
authors: Cherradi
authors: Lionel
authors: L
authors: Schiavolin
authors: Simon
authors: S
authors: Moussa
authors: Alaeddine
authors: A
authors: Meghraoui
authors: Ahmed
authors: A
authors: Meksem
authors: Latéfa
authors: L
authors: Biskri
authors: Mohamed
authors: M
authors: Azarkan
authors: Abdelmounaaïm
authors: A
authors: Allaoui
authors: Anne
authors: A
authors: Botteaux
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012475:Salmonella / Q000235:genetics / Q000378:metabolism; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D015007:Yersinia / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D050505:Mutant Proteins