# Probing mechanism and outcome of Chlamydia trachomatis response to antimicrobial insults

> **NIH NIH R21** · LSU HEALTH SCIENCES CENTER · 2020 · $183,750

## Abstract

Abstract
An obligate intracellular bacterium, Chlamydia trachomatis (Ct), is the leading sexually transmitted bacterial
infection worldwide. Chronic Ct infection leads to serious reproductive complications in women, including pelvic
inflammatory disease, pelvic pain, tubal infertility, and ectopic pregnancy. Recent compelling molecular data
support historical studies showing that Ct can establish chronic infections even with repeated antimicrobial
treatments. Yet, the mechanisms underpinning Ct adaptation, survival, and persistence during this onslaught
and host immune-imposed antimicrobial insults are unknown. To evaluate antimicrobial responses of intracellular
bacteria, it is desirable to establish quantitative relations between the fitness of growing or persisting bacteria
and the target host cells. These important relations are challenging to study during Chlamydia infection due to
the current limitations in techniques. To overcome this barrier, we have created a robust endogenous promoter-
fluorescent protein reporter system. Building on our recent success in probing the central aspect of a unique Ct
developmental cycle in situ, we hypothesize that Ct adapts to, and modulates, host cell metabolic pathways to
maintain viability during exposure to external and host immune-imposed antimicrobial insults. To test this
hypothesis, we propose two Aims: 1. To develop a novel in situ method using fluorescent protein expression
levels to quantify interchangeable Ct developmental cycle in live cells. This powerful tool will allow us to
quantitatively probe divergent chlamydial forms in a single Ct-containing vacuole and in a culture composed of
physiologically and phenotypically different cells; and 2. To characterize key signaling pathways, in Ct and its
host cells, that are vital to Ct adaptation and survival, in the presence of antimicrobial insults. Our innovative
studies will be achieved using advanced technologies, including gene reporter assays, florescence activated cell
sorting (FACS), and dual RNA sequencing (FACS-dual-RNAseq). Greater understanding of how Ct adapts,
survives, and persists in the presence of host immunity or antimicrobial agents, as well as reactivates from
persistence may provide important new insights into chlamydial pathogenesis. The findings from these studies
will provide the foundation to develop new treatment strategies targeting both acute and the chronic,
transmissible reservoirs of Ct infection.

## Key facts

- **NIH application ID:** 9938427
- **Project number:** 5R21AI146454-02
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** LI SHEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $183,750
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938427

## Citation

> US National Institutes of Health, RePORTER application 9938427, Probing mechanism and outcome of Chlamydia trachomatis response to antimicrobial insults (5R21AI146454-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9938427. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*