CpoS-Inc interactions facilitate host cell modulation during Chlamydia trachomatis infection

Xavier Tijerina; C A Jabeena; Robert Faris; Zhen Xu; Parker Smith; Nicholas J Schnicker; Mary M Weber

doi:10.1128/iai.00548-25

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CpoS-Inc interactions facilitate host cell modulation during Chlamydia trachomatis infection

Journal article

Open access

Peer reviewed

CpoS-Inc interactions facilitate host cell modulation during Chlamydia trachomatis infection

Xavier Tijerina, C A Jabeena, Robert Faris, Zhen Xu, Parker Smith, Nicholas J Schnicker and Mary M Weber

Infection and immunity, Vol.93(12), e0054825

12/16/2026

DOI: 10.1128/iai.00548-25

PMCID: PMC12707108

PMID: 41251378

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Abstract

Chlamydia trachomatis (C.t.), the leading bacterial cause of sexually transmitted infections, replicates within a unique intracellular compartment called the inclusion, which is modified by secreted proteins known as inclusion membrane (Inc) proteins. Here, we further characterize CpoS, an Inc protein previously shown to be critical for bacterial replication and inclusion development. We demonstrate that CpoS directly binds multiple coiled-coil region-containing Incs and engages Rab GTPases at a separate site. Notably, CpoS-InaC interactions facilitate the recruitment of select Arf GTPases to the inclusion membrane, while Rab recruitment occurs independently of these interactions. Biochemical and biophysical analyses revealed that Incs self-oligomerize to form higher-ordered structures, with CpoS adopting a tetrameric conformation resembling that of eukaryotic SNARE proteins. We propose that these assemblies serve as scaffolds to orchestrate vesicle docking, tethering, and fusion. Our findings highlight the intricate interplay between bacterial and host factors, revealing how C.t. leverages both Inc-Inc interactions and host protein engagement to manipulate vesicular trafficking and sustain infection.

CpoS

Chlamydia trachomatis

InaC

Inc-Inc interactions

T3S

Details

Title: Subtitle: CpoS-Inc interactions facilitate host cell modulation during Chlamydia trachomatis infection
Creators: Xavier Tijerina - University of Iowa
C A Jabeena - University of Iowa, Microbiology and Immunology
Robert Faris - University of Iowa
Zhen Xu - University of Iowa, Medicine Administration
Parker Smith - University of Iowa
Nicholas J Schnicker - University of Iowa
Mary M Weber - University of Iowa
Resource Type: Journal article
Publication Details: Infection and immunity, Vol.93(12), e0054825
DOI: 10.1128/iai.00548-25
PMID: 41251378
PMCID: PMC12707108
NLM abbreviation: Infect Immun
ISSN: 0019-9567
eISSN: 1098-5522
Publisher: American Society of Microbiology
Grant note: NIH: R01 AI150812, R01 AI155434, R61 AI179999, XT 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; XT T32 AI007511) and the University of Iowa Stead Family Scholars to M.M.W.
Language: English
Electronic publication date: 11/18/2025
Date published: 12/16/2026
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology; Medicine Administration
Record Identifier: 9985033765002771

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