# Characterizing the Function of Cyclic di-AMP on Chlamydial Growth and Differentiation

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $230,250

## Abstract

Project Summary: Characterizing the Function of Cyclic di-AMP on 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 bacterial causes. 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 suggests that
the presence of any particular gene(s) is critical, if not essential, for its growth and pathogenesis. Importantly,
Chlamydia also alternates 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 mechanistically study chlamydiae have significantly enhanced our understanding of this
pathogen. Related to this proposal is the observation that Chlamydia produces a second messenger
compound, cyclic di-AMP (c-di-AMP), that is known to activate host cell immune-signaling pathways.
Interestingly, c-di-AMP is typically produced in Gram-positive bacteria and mycobacteria to regulate aspects
of their physiology and pathogenesis, yet Chlamydia is a Gram-negative bacterium. We propose to investigate
why Chlamydia produces c-di-AMP and how it functions in the physiology of the organism. The first project
goal is to characterize using genetic techniques the effects of altering c-di-AMP production on Chlamydia
growth and developmental cycle progression. The second project goal is to identify genes that are regulated
by c-di-AMP. Results from the proposed studies will advance our understanding of the function of c-di-AMP
in chlamydial physiology and identify new targets for development of Chlamydia-specific treatments.

## Key facts

- **NIH application ID:** 10984811
- **Project number:** 1R21AI180574-01A1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Scot P Ouellette
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $230,250
- **Award type:** 1
- **Project period:** 2024-06-20 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984811

## Citation

> US National Institutes of Health, RePORTER application 10984811, Characterizing the Function of Cyclic di-AMP on Chlamydial Growth and Differentiation (1R21AI180574-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10984811. Licensed CC0.

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