Cell Host & Microbe
Volume 30, Issue 12, 14 December 2022, Pages 1685-1700.e10
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Article
Chlamydia repurposes the actin-binding protein EPS8 to disassemble epithelial tight junctions and promote infection

https://doi.org/10.1016/j.chom.2022.10.013Get rights and content
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Highlights

  • C. trachomatis transiently disrupts epithelial tight junctions

  • The effector TepP interacts with EPS8 and recruits it to nascent inclusions

  • TepP repurposes EPS8 to disrupt tight junctions and promote Chlamydia entry

  • TepP and EPS8 promote infection in mouse models of Chlamydia infection

Summary

Invasive microbial pathogens often disrupt epithelial barriers, yet the mechanisms used to dismantle tight junctions are poorly understood. Here, we show that the obligate pathogen Chlamydia trachomatis uses the effector protein TepP to transiently disassemble tight junctions early during infection. TepP alters the tyrosine phosphorylation status of host proteins involved in cytoskeletal regulation, including the filamentous actin-binding protein EPS8. We determined that TepP and EPS8 are necessary and sufficient to remodel tight junctions and that the ensuing disruption of epithelial barrier function promotes secondary invasion events. The genetic deletion of EPS8 renders epithelial cells and endometrial organoids resistant to TepP-mediated tight junction remodeling. Finally, TepP and EPS8 promote infection in murine models of infections, with TepP mutants displaying defects in ascension to the upper genital tract. These findings reveal a non-canonical function of EPS8 in the disassembly of epithelial junctions and an important role for Chlamydia pathogenesis.

Keywords

tight junctions
epithelia
infection
Chlamydia
upper genital tract
secreted effectors

Data and code availability

  • Phospho-proteomic datasets were deposited to MassIVE and will be available on the date of publication.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon request

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