# Antimicrobial activity of Escherichia coli Nissle 1917 microcin M

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $193,800

## Abstract

SUMMARY
Enterobacteriaceae are a family of Gram-negative bacteria that contains both commensals and pathogens
relevant to human health. Among the most prominent pathogens of this family is non-typhoidal Salmonella
enterica, a leading cause of infectious diarrhea worldwide. Key to this pathogen's success is its ability to elicit
intestinal inflammation, a host response that creates a hostile gut environment where many commensals are
depleted, but where Salmonella thrives, significantly increasing in abundance. During infection, pathogens must
acquire essential metal nutrients such as iron, an element that is highly limited by the host. In preliminary studies,
we found that the probiotic bacterium Escherichia coli Nissle 1917 can compete with Salmonella and other enteric
pathogens in the inflamed gut by producing antibacterial peptides termed microcins. In particular, we found that
Salmonella is susceptible to microcin M in iron-limited conditions and in the inflamed gut. The primary objective
of this application is to elucidate the antimicrobial activity of E. coli Nissle's microcin M (MccM) in vitro and in
vivo. Our central hypothesis is that conjugation to catecholate siderophores enables MccM to more selectively
target bacteria that express specific siderophore receptors in the Fe-limited host environment, without affecting
the gut microbiota at large. We plan to test our hypothesis and fulfill the objectives of this application by pursuing
the following two Specific Aims. In Aim 1, we will determine whether siderophore conjugation and siderophore
uptake machinery influences the antimicrobial activity of MccM, and we will identify putative cellular targets of
MccM activity by screening mutant libraries. Investigate the mechanisms underlying the selectivity of MccM
antimicrobial activity. In Aim 2, we will ascertain the antimicrobial activity of MccM against non-typhoidal
Salmonella in vivo, and we will determine whether administration of purified MccM perturbs the gut
microbiome.This work may lead to future development of microcins as therapeutics to limit colonization and
transmission of non-typhoidal Salmonella, and possibly other enteric pathogens and pathobionts, in an
environment that is otherwise favorable to their growth.

## Key facts

- **NIH application ID:** 10212238
- **Project number:** 5R21AI154644-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ELIZABETH M NOLAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,800
- **Award type:** 5
- **Project period:** 2020-07-07 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212238

## Citation

> US National Institutes of Health, RePORTER application 10212238, Antimicrobial activity of Escherichia coli Nissle 1917 microcin M (5R21AI154644-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10212238. Licensed CC0.

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