# Unraveling the role of protein phosphorylation in the regulation of development in Chlamydia trachomatis

> **NIH NIH R15** · SOUTHERN ILLINOIS UNIVERSITY CARBONDALE · 2020 · $27,500

## Abstract

ABSTRACT
Despite Chlamydia trachomatis being the leading cause of reportable bacterial sexually transmitted infections
(STIs) in the U.S. and worldwide, a significant knowledge gap exists regarding how Chlamydia regulates
and executes its essential developmental cycle. Disruption of development through novel inhibitors or
creation of mutants using state-of-the-art genetic approaches will facilitate advancement of antimicrobials or
production of live-attenuated vaccine strains. Improved methods for treating and preventing chlamydial STIs
will positively impact human health and the world economy by reducing rates of infertility, pelvic inflammatory
disease, ectopic pregnancies, HIV transmission, and HPV-associated cervical cancer.
Ser/Thr/Tyr protein phosphorylation is a dynamic and reversible mechanism for controlling protein function that
has been increasingly recognized as a widely-employed method for regulating bacterial growth and survival
and therefore pathogenesis. The overall objective of our R15 renewal application is to determine how
phosphorylation modulates chlamydial growth and development. We hypothesize that the chlamydial
kinases and phosphatases, including a phospho-regulated partner switching mechanism (PSM), orchestrate
essential changes in development and growth by converting signals into alterations in physiology by
modification of substrate function through reversible phosphorylation. Our premise is supported by the: 1)
presence of global protein phosphorylation in Chlamydia that is enriched in the elementary body (EB) form
compared to the reticulate body (RB) form, 2) conservation of the kinases and kinase substrates, a
phosphatase, and the PSM proteins across Chlamydia, 3) inhibition of growth when PknD (kinase) or Cpp1
(phosphatase) are inhibited, and 4) alteration in growth due to genetic modulation of PSM components.
Consequently, we predict that disruption of protein phosphorylation will inhibit bacterial growth.
We will address our hypothesis in three Aims: Aim 1. Defining how the pseudokinase Pkn5 impacts chlamydial
metabolism and growth, Aim 2. Delineating the role of Cpp1, a PP2C class phosphatase, in bacterial
development, and Aim 3. Elucidating the contribution of the PSM to growth rate. In addition, consistent with
the mission of AREA grants, the project will involve undergraduate and graduate students in research.
Collectively, our studies will: 1) address gaps in the understanding of chlamydial development, 2) identify novel
targets for drugs and potential inhibitors, and 3) further illuminate the importance of protein phosphorylation to
bacterial physiology and pathogenesis.

## Key facts

- **NIH application ID:** 10135184
- **Project number:** 3R15AI109566-02S1
- **Recipient organization:** SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
- **Principal Investigator:** Derek James Fisher
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $27,500
- **Award type:** 3
- **Project period:** 2018-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135184

## Citation

> US National Institutes of Health, RePORTER application 10135184, Unraveling the role of protein phosphorylation in the regulation of development in Chlamydia trachomatis (3R15AI109566-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10135184. Licensed CC0.

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