# Talking with Small Molecules: Corynebacteria in the Human Microbiome

> **NIH NIH R21** · PRINCETON UNIVERSITY · 2024 · $451,000

## Abstract

Project Summary & Abstract
 Bacteria communicate with their environment using a chemical language consisting of
secreted small molecules, also referred to as natural products or secondary metabolites. Nowhere
is this communication more relevant to human health than in the microbiome where hordes of
beneficial microbes and pathogens `talk' and compete amidst a cacophony of small molecule
exchanges. Corynebacteria are commensal residents of the skin and upper respiratory tract and
have recently emerged as opportunistic, multidrug-resistant pathogens. However, virtually
nothing is known about their secondary metabolomes and, thus, how they compete with other
microbes and interact with host cells. In the current application, we propose to characterize the
secondary metabolomes of three corynebacterial strains using high-throughput elicitor screening
(HiTES), a state-of-the-art chemical biology and natural product discovery approach that identifies
the small molecule products of silent or sparingly expressed biosynthetic genes. Specifically, we
plan to uncover the secondary metabolites that the three Corynebacteria use to compete with one
another in intra-genus chemical warfare, to antagonize Staphylococcus aureus in inter-genus
competition, and to modulate cytokine production by host cells in inter-kingdom associations.
Together, the results of this proposal will elucidate intra-genus, inter-genus and inter-kingdom
interactions by important and underexplored bacteria in the body. The feasibility for the proposed
exploratory grant is provided by recent application of the HiTES approach to streptococcal
bacteria in the microbiome. The proposed studies can therefore be completed in the two-year
period and thus shine light on the lifestyles of important microbiome members while at the same
time contributing important knowledge that can be used to develop therapies against
corynebacterial infections.

## Key facts

- **NIH application ID:** 11038877
- **Project number:** 1R21AT013123-01
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Mohammad R Seyedsayamdost
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2024-09-18 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11038877

## Citation

> US National Institutes of Health, RePORTER application 11038877, Talking with Small Molecules: Corynebacteria in the Human Microbiome (1R21AT013123-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11038877. Licensed CC0.

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