# Functional Analysis of the Clp Protease Systems in Chlamydial Growth and Differentiation

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $251,179

## Abstract

Project Summary: Functional analysis of the Clp Protease Systems in Chlamydial Growth and
Differentiation
 Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in
humans. In developed countries, Chlamydia trachomatis is the primary cause of bacterial sexually transmitted
infections (STI). Indeed, recent reports from the Centers for Disease Control highlight the increasing incidence
of STIs, with chlamydia infections consistently outpacing all other types. In developing countries, C.
trachomatis is not only a significant cause of STI, but it is also responsible for the primary cause of infectious
preventable blindness, trachoma. The major concern of chlamydial infections is that they are often
asymptomatic and undiagnosed, which can lead to chronic sequelae. These include pelvic inflammatory
disease, tubal factor infertility, and reactive arthritis for C. trachomatis. Consequently, chlamydial diseases
remain a significant burden on health care systems around the world.
 In adapting to obligate intracellular growth, Chlamydia has significantly reduced its genome size and
eliminated genes from various pathways as it relies on the host cell for its metabolic needs. This pathogen
has also adapted to alternate between different functional and morphological forms during its normal growth,
also referred to as its developmental cycle. These observations, combined with its obligate intracellular
dependence, makes Chlamydia a difficult organism with which to work. However, recent development of
genetic tools to study chlamydiae mechanistically have significantly enhanced our understanding of this
pathogen. This proposal applies a combination of these new genetic techniques and classical biochemical
studies to evaluate the role of conserved protease systems in chlamydial growth and pathogenesis. The
hypothesis of the proposed work is that Chlamydia uses two separate protease systems to regulate its growth
and transition between developmental forms as well as to respond to stress. Major goals of the proposal
include (i) characterizing the function of the different protease systems both in vitro and in vivo and (ii)
identifying and validating substrates of these protease systems. Results will advance our understanding of
this important pathogen and lead to the design of novel therapeutic agents that are specific for Chlamydia.
This in turn will allow for minimal effects on normal flora for patients receiving treatment for this highly prevalent
disease.

## Key facts

- **NIH application ID:** 10501967
- **Project number:** 1R01AI170688-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Derek James Fisher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $251,179
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501967

## Citation

> US National Institutes of Health, RePORTER application 10501967, Functional Analysis of the Clp Protease Systems in Chlamydial Growth and Differentiation (1R01AI170688-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10501967. Licensed CC0.

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