# Antibiotics from nose and throat commensals that impact pathogen colonization

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $497,393

## Abstract

Project Summary
The great promise of human microbiome research is that managing microbiome composition will prevent and
cure disease. To this end, our long-term goals are to identify molecular mechanisms that drive bacterial
community dynamics in nasal and skin microbiota and to uncover new antibiotics for controlling pathogen
colonization and infection. Previous research shows that nasal microbiome composition and Staphylococcus
aureus nasal colonization are strongly impacted by environmental factors, including other members of the
microbiome. However, the molecular underpinnings of this are largely unknown. This proposal focuses on
Propionibacterium species that colonize the skin and nasal passages of most adult humans. Our overarching
hypothesis is that cutaneous Propionibacterium species produce antibiotics that control colonization by and
proliferation of S. aureus and pathogenic Streptococcus species. Our preliminary data indicate that cutaneous
Propionibacterium encode a distinct set of biosynthetic gene clusters (BGCs) predicted to produce antibiotics.
We recently purified and structurally characterized one we call propimycin, a Propionibacterium-produced
thiopeptide with potent activity against S. aureus in vitro. Our objectives are to identify more of these antibiotics
and to define their role in shaping microbiome in vivo. Our rationale is that these Propionibacterium-produced
compounds are likely to be important drivers of skin/nasal microbiome composition and, thus, key to
developing new approaches to manage microbiome to promote health. To date, we have identified two
Propionibacterium antibiotic BGCs specifically induced by coculture with S. aureus, propimycin and a
nonribosomal peptide (NRP) that is widely distributed on human skin based on metagenomic data. We will use
chemistry, bioinformatic, transcriptomic and bacterial genetics approaches to achieve the Specific Aims of this
proposal: (1) determine the role of propimycin on human skin, focusing on skin follicles; (2A) purify and solve
the structure of the NRP, a second candidate Propionibacterium antibiotic predicted to have anti-S. aureus
activity; (2B) determine the mechanism of the NRP's increased transcription in response to Staphylococcus;
and (3) identify additional candidate Propionibacterium antibiotic BGCs expressed in the context of the skin or
nasal microbiome. Our strategy has four main innovations: (1) doing molecular experimental work in cutaneous
Propionibacterium, which are recalcitrant to genetic manipulation; (2) using sebaceous plugs from human skin
follicles to develop ex vivo assays to assess the impact of Propionibacterium antibiotics on S. aureus; (3)
coupling a genetic screen in a heterologous system with next-gen-sequencing-based identification of
promoters bound by candidate Propionibacterium acnes transcriptional regulators; and (4) using interactions
between commensal Propionibacterium and the pathogens S. aureus and S. pneumoniae to uncover
molecu...

## Key facts

- **NIH application ID:** 10071816
- **Project number:** 7R01AI101018-08
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** MICHAEL ANDREW FISCHBACH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $497,393
- **Award type:** 7
- **Project period:** 2012-08-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071816

## Citation

> US National Institutes of Health, RePORTER application 10071816, Antibiotics from nose and throat commensals that impact pathogen colonization (7R01AI101018-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071816. Licensed CC0.

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