# Microbial Ecology-Guided Discovery of Antibacterial Drugs

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $664,819

## Abstract

Project Summary/Abstract
Multidrug-resistant bacteria are an increasing health threat. Most new antibacterial agents are natural products
that are made by bacteria, or their synthetic derivatives. This is because, over evolutionary time, bacteria gain
the ability to synthesize small molecules that very selectively target essential processes in other bacteria. One
problem in identifying good antibacterial agents that are relatively nontoxic to people is that early drug
discovery assays cannot determine whether compounds are truly selective until well into the drug development
process. There is no reason that randomly cultivated bacteria from the environment would produce chemicals
that are benign in humans, yet lethal to competing bacteria. Finding those compounds, or improving existing
compounds to minimize toxicity and improve antibacterial activity, requires a significant investment. Here, we
propose to examine symbiotic bacteria that are compatible with animal physiology, and for which evolution
favors the production of selective antibacterial agents. The bacteria are enriched within animal hosts, where
they produce hundreds or perhaps thousands of small molecule natural products. One of the main ecological
roles of the symbiotic bacteria is likely to clear other bacteria from the host. Proof-of-concept experiments
demonstrate that the bacteria produce nontoxic compounds that very selectively target human pathogens,
including some of the most lethal bacterial pathogens that infect humans. In this program, we will optimize
identified, chemically novel antibacterial compounds by understanding their mechanisms of action and by
investigating and improving their existing properties further through chemical synthesis. Further, we will
continue to identify and characterize promising new antibacterial agents that are previously unknown to
science. Our long-term goal is to provide a novel pipeline of new antibacterial agents to combat multidrug
resistance.

## Key facts

- **NIH application ID:** 10446908
- **Project number:** 1R01AI162943-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Eric W Schmidt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $664,819
- **Award type:** 1
- **Project period:** 2022-02-07 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446908

## Citation

> US National Institutes of Health, RePORTER application 10446908, Microbial Ecology-Guided Discovery of Antibacterial Drugs (1R01AI162943-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10446908. Licensed CC0.

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