Abstract
In Gram-negative bacterial pathogens, specialized chaperones bind to secreted effector proteins and maintain them in a partially unfolded form competent for translocation by type III secretion systems/injectisomes. How diverse sets of effector-chaperone complexes are recognized by injectisomes is unclear. Here we describe a new mechanism of effector-chaperone recognition by the Chlamydia injectisome, a unique and ancestral line of these evolutionarily conserved secretion systems. By yeast two-hybrid analysis we identified networks of Chlamydia-specific proteins that interacted with the basal structure of the injectisome, including two hubs of protein-protein interactions that linked known secreted effector proteins to CdsQ, the putative cytoplasmic C-ring component of the secretion apparatus. One of these protein-interaction hubs is defined by Ct260/Mcsc (Multiple cargo secretion chaperone). Mcsc binds to and stabilizes at least two secreted hydrophobic proteins, Cap1 and Ct618, that localize to the membrane of the pathogenic vacuole (“inclusion”). The resulting complexes bind to CdsQ, suggesting that in Chlamydia, the C-ring of the injectisome mediates the recognition of a subset of inclusion membrane proteins in complex with their chaperone. The selective recognition of inclusion membrane proteins by chaperones may provide a mechanism to co-ordinate the translocation of subsets of inclusion membrane proteins at different stages in infection.
Highlights
The obligate, intracellular bacterium Chlamydia trachomatis infects the epithelium of the genital tract and conjunctivae, causing a wide range of ailments including the blinding disease trachoma, conjunctivitis, salpingitis, pelvic inflammatory disease and infertility [1]
CdsQ, a conserved structural component predicted to be at the base of the injectisome, interacted with multiple proteins, including a new chaperone that binds to and stabilizes secretory cargo destined for the membrane of the pathogenic vacuole
These results suggest that the base of the secretion apparatus serves as a docking site for a chaperone and a subset of chaperone-cargo complexes
Summary
The obligate, intracellular bacterium Chlamydia trachomatis infects the epithelium of the genital tract and conjunctivae, causing a wide range of ailments including the blinding disease trachoma, conjunctivitis, salpingitis, pelvic inflammatory disease and infertility [1]. Chlamydiae display an elaborate life cycle beginning with the attachment of an elementary body (EB), the infectious form of the bacteria, to the surface of epithelial cells [2]. The RB-containing vacuole is rapidly segregated from normal endosomal maturation pathways to generate a membrane-bound ‘‘inclusion’’ [3]. Chlamydial replication becomes asynchronous to yield both RBs and EBs. Eventually, most of the cytoplasmic space of the host cell is occupied by the inclusion and EBs exit the host cell to infect adjacent cells [4]
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