# The role of secreted effector proteins in Chlamydia trachomatis invasion

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $490,102

## Abstract

Project Summary
Chlamydia trachomatis (C.t.) is the leading cause of non-congenital blindness and the most prevalent sexually
transmitted bacterial infection in the world, which if left untreated can result in severe consequences. All
chlamydiae are obligate intracellular bacteria and thus gaining entry into a host cell is essential for the pathogen
to complete its replicative cycle and proliferate. Despite the critical nature of the invasion process, the molecular
mechanisms and details regarding how C.t. forces its way into non-phagocytic cells remains a large knowledge
gap. A major premise of the current model suggests that invasion is facilitated by delivery of prepackaged
conventional type III secretion system (cT3SS) effector proteins into the host cell prior to pathogen entry. We
hypothesize that a subset of these cT3SS effectors coordinate active subversion of the host cytoskeleton through
direct manipulation of key regulators of actin dynamics. New data from our laboratory indicates that the cT3SS
effector protein TmeA binds to the nucleation promoting factor N-WASP, both of which we show are essential
for invasion. In Aim 1, we will mechanistically determine how TmeA regulates N-WASP and determine whether
this interaction promotes key membrane features that likely aid in bacterial entry such as; membrane ruffling,
pedestal formation, and filopodial dynamics. Given the essential nature of invasion to bacterial proliferation and
survival, C.t. likely employs multiple measures for invasion. In Aim 2, we will evaluate the complex interplay
between TarP, TepP, and TmeA and reveal the ultimate molecular effects of their effector function and describe
how the seemingly disparate pathways targeted by these effectors converge to assure chlamydial invasion.
Furthermore, we will determine whether other cT3SS effectors, only expressed in the invasive EB form of
chlamydia, are necessary for invasion of non-phagocytic cells. Detailed characterization of the bacterial and host
proteins required to promote reorganization of the actin cytoskeleton during C.t. invasion will provide a holistic
view of how intracellular pathogens, such as C.t., coordinate subversion of cytoskeletal regulators to invade host
cells.

## Key facts

- **NIH application ID:** 10899746
- **Project number:** 5R01AI155434-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Mary Weber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $490,102
- **Award type:** 5
- **Project period:** 2020-09-22 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899746

## Citation

> US National Institutes of Health, RePORTER application 10899746, The role of secreted effector proteins in Chlamydia trachomatis invasion (5R01AI155434-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10899746. Licensed CC0.

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