# Genomics-Assisted Antibiotic Discovery from Unprecedented Microbes of the Great Salt Lake

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $622,123

## Abstract

PROJECT SUMMARY
With antibiotic resistance mechanisms spreading rapidly among disease-causing bacteria, our ability to treat
common infections is becoming increasingly difficult. To combat resistance, we desperately need new antibiotic
agents possessing novel modes of action. Natural products, also called secondary metabolites, are small
molecules produced in nature. Secondary metabolites play pivotal roles in many cellular processes and
represent some of the most important pharmaceutical agents in human health care. This especially holds true in
the antibiotic arena as a majority of the clinically prescribed antibiotics are natural products or derivatives thereof
and have been isolated primarily from soil-dwelling bacteria. In recognition that microorganisms have been the
most prolific source of new antibiotics, this project turns back to Nature to exploit the completely unexplored
hypersaline microbes in the Great Salt Lake as a resource for drug discovery. Our observations are that
environmental pressures influence the structural diversity of compounds produced in Nature and microorganisms
thriving in extreme environments often produce chemical agents not observed in their terrestrial counterparts.
The Great Salt Lake, also recognized as “America's Dead Sea”, is an endorheic (fully isolated) hypersaline lake
located near the University of Utah in Salt Lake City, Utah. While seawater has an average salinity of ~3.3%, the
Great Salt Lake ranges between 8-28%. Our preliminary data demonstrate that the unexplored hypersaline
microorganisms of the Great Salt Lake possess antimicrobial activity against Gram-negative and Gram-positive
bacterial pathogens, produce metabolites containing molecular scaffolds never before observed, and their
genomes contain unprecedented biosynthetic machinery. Thus, these microbes serve as an ideal resource for
the discovery of new antimicrobial agents possessing novel modes of action. To access and develop these
agents, we have developed an integrated project that will leverage the strengths of our collaborative team
including expertise in natural products isolation and structural elucidation, microbial biochemistry, genome
mining, bioinformatics and bioengineering of recombinant natural products. From this project, unique antibiotic
agents can be discovered along with information defining their biosynthetic pathways, their molecular targets,
and likely other mechanisms of drug resistance. To exploit this novel resource, our specific aims will focus on:
1) Creating a hypersaline microbial library from sediment collected from the Great Salt Lake and screening the
isolates using innovative methods for antimicrobial activity; 2) Identifying and validating new antibiotic agents
using chemical and molecular networks; and 3) Identifying the biosynthetic machinery and molecular targets of
the newly discovery antibiotic agents using genomic and bioinformatic approaches.

## Key facts

- **NIH application ID:** 10448339
- **Project number:** 5R01AI155694-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Jaclyn Marie Winter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $622,123
- **Award type:** 5
- **Project period:** 2021-07-12 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448339

## Citation

> US National Institutes of Health, RePORTER application 10448339, Genomics-Assisted Antibiotic Discovery from Unprecedented Microbes of the Great Salt Lake (5R01AI155694-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10448339. Licensed CC0.

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