Abstract
BackgroundChlamydia spp. are believed to use a conserved virulence factor called type III secretion (T3S) to facilitate the delivery of effector proteins from the bacterial pathogen to the host cell. Important early effector proteins of the type III secretion system (T3SS) are a class of proteins called the translocators. The translocator proteins insert into the host cell membrane to form a pore, allowing the injectisome to dock onto the host cell to facilitate translocation of effectors. CopB is a predicted hydrophobic translocator protein within the chlamydial T3SS.ResultsIn this study, we identified a novel interaction between the hydrophobic translocator, CopB, and the putative filament protein, CdsF. Furthermore, we identified a conserved PxLxxP motif in CopB (amino acid residues 166–171), which is required for interaction with its cognate chaperone, LcrH_1. Using a synthetic peptide derived from the chaperone binding motif of CopB, we were able to block the LcrH_1 interaction with either CopB or CopD; this CopB peptide was capable of inhibiting C. pneumoniae infection of HeLa cells at micromolar concentrations. An antibody raised against the N-terminus of CopB was able to inhibit C. pneumoniae infection of HeLa cells.ConclusionThe inhibition of the LcrH_1:CopB interaction with a cognate peptide and subsequent inhibition of host cell infection provides strong evidence that T3S is an essential virulence factor for chlamydial infection and pathogenesis. Together, these results support that CopB plays the role of a hydrophobic translocator.
Highlights
Chlamydia spp. are believed to use a conserved virulence factor called type III secretion (T3S) to facilitate the delivery of effector proteins from the bacterial pathogen to the host cell
We identify a CopB epitope which is immunogenic and elicits neutralizing antibodies that block C. pneumoniae infection supporting an essential role for CopB in the infection of host cells
Bioinformatic analysis of Chlamydia outer protein (Cop) B Translocator proteins have a conserved function across numerous bacterial species, facilitating the translocation of effector proteins from the bacterial cytosol to the host cell cytoplasm through formation of pores within the host cell membrane
Summary
Chlamydia spp. are believed to use a conserved virulence factor called type III secretion (T3S) to facilitate the delivery of effector proteins from the bacterial pathogen to the host cell. Important early effector proteins of the type III secretion system (T3SS) are a class of proteins called the translocators. C. pneumoniae infections have been associated with asthma exacerbations, Bulir et al BMC Microbiology (2015) 15:163 components, which include the cytoplasmic C-ring, the inner and outer membrane rings, the needle complex, and needle-tip complex [8,9,10, 12]. Each of these components display numerous essential protein-protein interactions. Despite the identification and characterization of many putative T3S proteins, it remains unclear whether Chlamydia truly has a functional T3SS, and whether it plays a role in replication and survival given the absence of a robust genetic manipulation system for gene knockouts [13]
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