# Factors that modulate the deleterious effect of ammonia generation by chlamydial tryptophan synthase

> **NIH NIH R21** · LSU HEALTH SCIENCES CENTER · 2021 · $183,750

## Abstract

Genital Chlamydia trachomatis! (CT) infections are a major public health concern that can adversely affect
reproductive health and neonate survival. Interferon gamma (IFNg) is proposed to protect against CT infection
by inducing the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1). The ensuing depletion
of tryptophan starves CT of this essential amino-acid leading to bacterial eradication. By expressing the
chlamydial enzyme tryptophan synthase (TS), genital serovars of CT can escape the effects of IFNg if the
microbial metabolite indole is present in the infection microenvironment. TS can salvage indole within the
chlamydial inclusion to generate tryptophan. TS expression is tightly regulated by the tryptophan operon
repressor (TrpR), which permits transcription of the operon only when tryptophan is absent. We recently
discovered that indole derivatives produced by the gut microbiome, termed TrpR de-repressors, rapidly induce
the expression of chlamydial TS. Further, when TS is expressed in the absence of indole, the enzyme rapidly
deaminates serine to generate ammonia (NH3), a known bactericidal compound. While evaluating the effect of
TrpR de-repressors on different chlamydial serovars, we discovered that although de-repression was equally
efficient between them, the production of NH3 varied dramatically. Using a combination of approaches, here we
propose to: 1) Identify methods by which CT can assimilate NH3 produced by TS; and 2) Determine whether
sequence differences in TS between serovars determines their catalytic properties vis-à-vis ammonia
generation. The outcome of our findings will permit the design of novel pharmacological approaches against
chlamydial infection by augmenting the effect of protective host responses.

## Key facts

- **NIH application ID:** 10198719
- **Project number:** 5R21AI153774-02
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Ashok A Aiyar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $183,750
- **Award type:** 5
- **Project period:** 2020-06-19 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198719

## Citation

> US National Institutes of Health, RePORTER application 10198719, Factors that modulate the deleterious effect of ammonia generation by chlamydial tryptophan synthase (5R21AI153774-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10198719. Licensed CC0.

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