# Chlamydial invasion of non-phagocytic cells

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $381,250

## Abstract

PROJECT SUMMARY
Chlamydia trachomatis is the etiologic agent of the most prevalent sexually transmitted infection (STI) in
industrialized nations and the blinding condition, trachoma, in under-developed countries. There is an
estimated 93 million new reported cases of Chlamydia STI annually worldwide. Trachoma affects
approximately 150 million individuals, predominantly women and children. The pathologic hallmark of both
diseases is the scarring the results from chronic inflammation; and inflammation at the very early stages of
infection is initiated by infection of epithelial cells, and sustained by active bacterial replication and
dissemination along the genital and ocular mucosae.
 Chlamydia is a Gram-negative obligate intracellular pathogen, which means that it requires an intracellular
environment for its survival and replication. Hence, invasion of a permissive host cell is paramount to its
survival and pathogenesis. In vivo, the primary target is the epithelial cells that line the ocular and genital
mucosae. Our overarching hypothesis is that invasion is a Chlamydia-driven process. This pathogen has
evolved mechanisms of manipulating the host cell actin cytoskeleton of to induce its uptake, leading to the
formation of cell surface structures designed to engulf the bacteria. Invasion involves a number of signaling
pathways that in normal cells play a role in regulating actin cytoskeleton dynamics. The bacteria turns on the
machinery at its site of adherence, with the location of actin remodeling determined by the restricted
translocation of a chlamydial virulence protein called TarP to the cytosolic side of the host cell plasma
membrane. TarP recruits a number of signaling molecules to initiate the remodeling of the actin cytoskeleton,
followed by the engulfment of the pathogen.
 Once inside the cell, the pathogen has the opportunity to hijack other cellular processes, including the
initiation of inflammation, which when sustained leads to tissue damage and scarring of the ocular conjunctiva
the genital tract resulting in infertility. Thus, the ability of Chlamydia to cause disease starts with invasion.
While we have a better understanding of TarP function during invasion, mechanistic details on how it is
regulated is sparse. This application will investigate the role of mechanotransduction in regulating TarP
interactions with host signaling molecules. The following Specific Aims will be addressed. I) To identify the
mechanism and significance of TarP mechanosensing in invasion; II) To define the myosin II-regulated
components of the chlamydial invasome; and III) To determine the mechanism of uptake post-actin
recruitment. The goal is to obtain a detailed understanding of TarP function and regulation in order to guide
rational drug and vaccine designs to combat Chlamydia infections.

## Key facts

- **NIH application ID:** 10078928
- **Project number:** 5R01AI065545-10
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** REY A CARABEO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2005-07-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10078928

## Citation

> US National Institutes of Health, RePORTER application 10078928, Chlamydial invasion of non-phagocytic cells (5R01AI065545-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10078928. Licensed CC0.

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