Chlamydia Outer Protein (Cop) B from Chlamydia pneumoniae possesses characteristic features of a type III secretion (T3S) translocator protein.

Autor: Bulir DC; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. bulirdc@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. bulirdc@mcmaster.ca., Waltho DA; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. dwalt077@uottawa.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. dwalt077@uottawa.ca., Stone CB; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. stonech@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. stonech@mcmaster.ca., Liang S; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. liangsn@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. liangsn@mcmaster.ca., Chiang CK; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. chianc@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. chianc@mcmaster.ca., Mwawasi KA; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. mwawask@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. mwawask@mcmaster.ca., Nelson JC; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. nelsojc@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. nelsojc@mcmaster.ca., Zhang SW; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. stevenwzz@hotmail.com.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. stevenwzz@hotmail.com., Mihalco SP; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. mihalcs@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. mihalcs@mcmaster.ca., Scinocca ZC; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. scinoczc@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. scinoczc@mcmaster.ca., Mahony JB; M. G. DeGroote Institute for Infectious Disease Research, Faculty of Health Sciences and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. mahonyj@mcmaster.ca.; Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare, Hamilton, ON, Canada. mahonyj@mcmaster.ca.; Regional Virology Laboratory, St. Joseph's Healthcare, 50 Charlton Ave. E, Hamilton, ON, L8N 4A6, Canada. mahonyj@mcmaster.ca.
Jazyk: angličtina
Zdroj: BMC microbiology [BMC Microbiol] 2015 Aug 14; Vol. 15, pp. 163. Date of Electronic Publication: 2015 Aug 14.
DOI: 10.1186/s12866-015-0498-1
Abstrakt: Background: 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. 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.
Results: In 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.
Conclusion: The 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.
Databáze: MEDLINE