Identification of novel type III secretion chaperone-substrate complexes of Chlamydia trachomatis

PLoS One. 2013;8(2):e56292. doi: 10.1371/journal.pone.0056292. Epub 2013 Feb 19.

Abstract

Chlamydia trachomatis is an obligate intracellular bacterial pathogen of humans that uses a type III secretion (T3S) system to manipulate host cells through the delivery of effector proteins into their cytosol and membranes. The function of T3S systems depends on small bacterial cytosolic chaperone-like proteins, which bind T3S substrates and ensure their appropriate secretion. To find novel T3S chaperone-substrate complexes of C. trachomatis we first searched its genome for genes encoding proteins with features of T3S chaperones. We then systematically tested for interactions between candidate chaperones and chlamydial T3S substrates by bacterial two-hybrid. This revealed interactions between Slc1 (a known T3S chaperone) or CT584 and several T3S substrates. Co-immunoprecipitation after protein expression in Yersinia enterocolitica and protein overlay binding assays indicated that Slc1 interacted with the N-terminal region of the known T3S substrates Tarp (a previously described substrate of Slc1), CT694, and CT695, and that CT584 interacted with a central region of CT082, which we identified as a C. trachomatis T3S substrate using Y. enterocolitica as a heterologous system. Further T3S assays in Yersinia indicated that Slc1 or CT584 increased the amount of secreted Tarp, CT694, and CT695, or CT082, respectively. Expression of CT584 increased the intra-bacterial stability of CT082, while Slc1 did not affect the stability of its substrates. Overall, this indicated that in C. trachomatis Slc1 is a chaperone of multiple T3S substrates and that CT584 is a chaperone of the newly identified T3S substrate CT082.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Secretion Systems*
  • Chlamydia trachomatis / metabolism*
  • Gene Expression Regulation, Bacterial
  • HeLa Cells
  • Humans
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Stability
  • Two-Hybrid System Techniques
  • Yersinia enterocolitica

Substances

  • Bacterial Proteins
  • Bacterial Secretion Systems
  • Molecular Chaperones

Grants and funding

This work was supported by Fundação para a Ciência e a Tecnologia (FCT) through grants PEst-OE/EQB/LA0004/2011, PTDC/SAU-MII/099623/2008, and ERA-PTG/0005/2010 (in the frame of ERA-NET PathoGenoMics), by the European Commission through a Marie Curie European Re-integration Grant (PERG03-GA-2008-230954), and by a European Society for Clinical Microbiology and Infectious Diseases (ESCMID) research grant. FA holds PhD fellowship SFRH/BD/73545/2010 from FCT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.