# Modulation of the antimicrobial content of myxobacteria outer membrane vesicles in response to varying LPS polysaccharide structures.

> **NIH NIH P20** · UNIVERSITY OF MISSISSIPPI · 2020 · $253,534

## Abstract

Project Summary
The 30-year absence of a newly discovered clinically approved natural product-derived antibiotic demonstrates
the dire need for unique methods to access new antimicrobial scaffolds and activities. However, the recent surge
in scrutiny of microbial genomes provides evidence to indicate that an abundance of chemical scaffolds hidden
within nascent biosynthetic pathways (BSPs) remain undiscovered. Predatory myxobacteria have contributed
over 600 distinct natural products to the microbial chemical space including 42 novel scaffolds of which 29 exhibit
antibacterial or antifungal activities in the last 6 years alone. Myxobacteria exemplify the abundance of untapped
chemical space with large bacterial genomes replete with BSPs that typically account for 10% of their total
genomic content. However, unlike natural product isolations from other organisms such as plants or marine
sponges sequestered directly from competitive surroundings, bacterial extracts from natural environments both
marine and terrestrial often omit chemical entities below current detection levels. Instead, bacterial natural
products are predominately isolated from axenic cultivation of a producing species removed from community
maintenance and competition. We hypothesize that myxobacterial cultivation conditions that induce predation
either through supplementation with isolated exopolysaccharide (EPS) from prey bacteria or non-axenic, co-
cultivation with known quarry will result in production of antimicrobial new chemical entities (NCEs). We will
molecular network mass spectrometry datasets collected from the cultivation of 12 myxobacteria using these
conditions facilitated by the Global Natural Products Social Molecular Networking (GNPS) open access platform
to efficiently identify resulting NCEs for further antimicrobial assessment. These molecular networking efforts will
generate 1,008 datasets that will represent the chemical space available to myxobacteria when exposed to prey
or isolated prey EPS and significantly benefit dereplication and discovery efforts. Our conservative expectation
of 1-2 NCEs per investigated myxobacterial predator would provide a total of 13-26 potential antimicrobial NCEs
upon completion of the proposed research.

## Key facts

- **NIH application ID:** 9853997
- **Project number:** 1P20GM130460-01A1
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI
- **Principal Investigator:** David Cole Stevens
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $253,534
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853997

## Citation

> US National Institutes of Health, RePORTER application 9853997, Modulation of the antimicrobial content of myxobacteria outer membrane vesicles in response to varying LPS polysaccharide structures. (1P20GM130460-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853997. Licensed CC0.

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