Chlamydia repurposes the actin-binding protein EPS8 to disassemble epithelial tight junctions and promote infection.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Dolat, L; Carpenter, VK; Chen, Y-S; Suzuki, M; Smith, EP; Kuddar, O; Valdivia, RH

Published Date

  • December 14, 2022

Published In

Volume / Issue

  • 30 / 12

Start / End Page

  • 1685 - 1700.e10

PubMed ID

  • 36395759

Pubmed Central ID

  • PMC9793342

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2022.10.013


  • eng

Conference Location

  • United States