Secretion of the chlamydial virulence factor CPAF requires the Sec-dependent pathway

Ding Chen, Lei Lei, Chunxue Lu, Rhonda Flores, Matthew P. DeLisa, Tucker C. Roberts, Floyd E. Romesberg, Guangming Zhong

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

The chlamydial protease/proteasome-like activity factor (CPAF) is secreted into the host cytosol to degrade various host factors that benefit chlamydial intracellular survival. Although the full-length CPAF is predicted to contain a putative signal peptide at its N terminus, the secretion pathway of CPAF is still unknown. Here, we have provided experimental evidence that the N-terminal sequence covering the M1-G31 region was cleaved from CPAF during chlamydial infection. The CPAF N-terminal sequence, when expressed in a phoA gene fusion construct, was able to direct the export of the mature PhoA protein across the inner membrane of wild-type Escherichia coli. However, E. coli mutants deficient in SecB failed to support the CPAF signal-peptide-directed secretion of PhoA. Since native PhoA secretion was known to be independent of SecB, this SecB dependence must be rendered by the CPAF leader peptide. Furthermore, lack of SecY function also blocked the CPAF signal-peptide-directed secretion of PhoA. Most importantly, CPAF secretion into the host cell cytosol during chlamydial infection was selectively inhibited by an inhibitor specifically targeting type I signal peptidase but not by a type III secretion-system-specific inhibitor. Together, these observations have demonstrated that the chlamydial virulence factor CPAF relies on Sec-dependent transport for crossing the chlamydial inner membrane, which has provided essential information for further delineating the pathways of CPAF action and understanding chlamydial pathogenic mechanisms.

Original languageEnglish (US)
Pages (from-to)3031-3040
Number of pages10
JournalMicrobiology
Volume156
Issue number10
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Microbiology

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    Chen, D., Lei, L., Lu, C., Flores, R., DeLisa, M. P., Roberts, T. C., Romesberg, F. E., & Zhong, G. (2010). Secretion of the chlamydial virulence factor CPAF requires the Sec-dependent pathway. Microbiology, 156(10), 3031-3040. https://doi.org/10.1099/mic.0.040527-0