# Subversion of the host cell cytoskeleton and innate immunity by Chlamydia trachomatis

> **NIH NIH F32** · DUKE UNIVERSITY · 2020 · $67,446

## Abstract

Abstract
Background: The Gram-negative obligate intracellular bacterium Chlamydia trachomatis infects
epithelia of the urogenital tract causing tissue damage, pelvic inflammatory disease and infertility.
Chlamydiae utilize a type III secretion (T3S) system to deliver a network of effectors to host
epithelial cells to establish an infection. How the T3S effectors subvert the host cell machinery
and regulate the innate immune response is poorly understood.
Broad, long-term objective: The objective of this proposal is to define at the molecular level how
a network of Chlamydia effectors delivered during early infection regulate the host epithelial cell
cytoskeleton, tissue architecture and the innate immune response in a novel three-dimensional
endometrial organoid (EO) system. This new infection model is ideal for studying Chlamydia
infection – fully differentiated and diverse polarized epithelia positioned in a 3D environment,
which mimics tissue architecture in vivo and betters recapitulates the organization of the
cytoskeleton and interaction with immune cells.
Specific aims: Aim 1 of this study is to functionally characterize the EO infection model, examine
how the T3S effector TepP affects epithelial integrity and immune cell recruitment, and define
cell-type-specific responses to infection. Aim 2 investigates how an early T3S effector network
cooperatively subverts host cell signaling pathways to promote inclusion biogenesis, maturation
and bacterial replication.
Method: I will combine a targeted gene disruption technique using group II intronic insertion to
generate Chlamydia T3S effector deficient strains, a three-dimensional organoid infection model,
immune cell recruitment assays, and high-resolution light microscopy. Biochemical techniques
including affinity purification coupled to mass-spectrometry will identify host targets of T3S
effectors.
Health-relatedness: Chlamydia infections are the leading cause of preventable blindness in the
developing world and the most common sexually transmitted bacterial pathogen. Repeated
infections lead to chronic immune cell infiltration that can result in tissue scarring and damage.
Significantly, infections can lead to severe sequelae and are associated with cervical and ovarian
cancer, yet the mechanisms by which Chlamydia disrupts epithelial tissue structure, function and
growth are poorly understood. The proposed research utilizes cutting-edge infection models and
new genetic techniques to understand how Chlamydia virulence factors target host cell factors to
disrupt epithelial tissue functions and regulate the innate immune response.

## Key facts

- **NIH application ID:** 9830500
- **Project number:** 5F32AI138372-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Lee Dolat
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830500

## Citation

> US National Institutes of Health, RePORTER application 9830500, Subversion of the host cell cytoskeleton and innate immunity by Chlamydia trachomatis (5F32AI138372-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9830500. Licensed CC0.

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