Chlamydia trachomatis TmeA promotes pedestal-like structure formation through N-WASP and TOCA-1 interactions

Alix McCullough; C A Jabeena; Steve Huang; Brianna Steiert; Robert Faris; Mary M Weber

doi:10.1128/msphere.00101-25

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Chlamydia trachomatis TmeA promotes pedestal-like structure formation through N-WASP and TOCA-1 interactions

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Chlamydia trachomatis TmeA promotes pedestal-like structure formation through N-WASP and TOCA-1 interactions

Alix McCullough, C A Jabeena, Steve Huang, Brianna Steiert, Robert Faris and Mary M Weber

mSphere, Vol.10(5), e00101-25

05/27/2025

DOI: 10.1128/msphere.00101-25

PMCID: PMC12108077

PMID: 40231845

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Abstract

Chlamydia trachomatis (C.t.) is the causative agent of several human diseases, including the sexually transmitted infection chlamydia and the eye infection trachoma. As an obligate intracellular bacterial pathogen, invasion is critical for establishing infection and subsequent pathogenesis. During invasion, C.t. secretes effector proteins via its type III secretion system (T3SS), which manipulate host actin cytoskeletal regulation to promote bacterial entry. Previous studies identified the T3SS effector protein TmeA as a key factor in C.t. invasion, as it recruits and activates N-WASP. This interaction, in turn, activates the Arp2/3 complex, driving cytoskeletal rearrangements at the invasion site to drive C.t. uptake. In this study, we define the role of the N-WASP CRIB domain in mediating this interaction and demonstrate that TmeA functions as a mimic of Cdc42 as part of its established role in activating N-WASP. Additionally, we identified TOCA-1 as another host protein that directly interacts with TmeA. In other bacterial pathogens, notably an enterohemorrhagic E. coli, N-WASP and TOCA-1 are hijacked to mediate pedestal formation. Using siRNA-mediated knockdown of N-WASP and TOCA-1, followed by transmission electron microscopy, we found that both proteins are important for C.t.-mediated pedestal-like structure formation. Collectively, these findings expand our understanding of the intricacies of C.t. invasion, highlighting how TmeA-mediated interactions with N-WASP and TOCA-1 contribute to pedestal-like structure formation, which may represent an early step in C.t. infection.

pedestal

TOCA-1

TmeA

invasion

T3SS

Chlamydia trachomatis

N-WASP

Details

Title: Subtitle: Chlamydia trachomatis TmeA promotes pedestal-like structure formation through N-WASP and TOCA-1 interactions
Creators: Alix McCullough - University of Iowa
C A Jabeena - University of Iowa, Microbiology and Immunology
Steve Huang - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Brianna Steiert - Washington State University
Robert Faris - University of Iowa
Mary M Weber - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: mSphere, Vol.10(5), e00101-25
DOI: 10.1128/msphere.00101-25
PMID: 40231845
PMCID: PMC12108077
NLM abbreviation: mSphere
ISSN: 2379-5042
eISSN: 2379-5042
Publisher: AMER SOC MICROBIOLOGY
Grant note: NIH: R01 AI150812, R01 AI155434, R61 AI179999, T32 AI007511 University of Iowa Stead Family Scholars
We acknowledge grant support from the NIH (M.M.W., R01 AI150812, R01 AI155434, and R61 AI179999; A.M., T32 AI007511, B.S. T32 AI007511) and the University of Iowa Stead Family Scholars to M.M.W.
Language: English
Electronic publication date: 04/15/2025
Date published: 05/27/2025
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9984811206602771

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