# Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota

> **NIH NIH R35** · BAYLOR COLLEGE OF MEDICINE · 2022 · $400,000

## Abstract

The objective unifying our two areas of NIGMS-funded research is to identify molecular mechanisms underlying
microbe-microbe and microbe-host interactions involving D. pigrum and nasal Corynebacterium species that
shape the human nasal microbiota. Evidence indicates that Corynebacterium species and Dolosigranulum
pigrum play key roles in structuring a nasal microbiota beneficial to human health. For example, people with high
levels of Corynebacterium and/or D. pigrum in their nasal microbiota are less likely to be colonized by pathobionts
and, therefore, are at lower risk of invasive infections in other parts of their bodies. Similarly, nasal microbiota
dominated by Corynebacterium/D. pigrum are often associated with health rather than with diseases such as
otitis media and pneumonia. Our overarching hypothesis is that interactions between D. pigrum and
Corynebacterium species drive a beneficial health-promoting human nasal microbiota. A central goal of this
research is to shift from correlations in compositional data to causation by identifying molecular mechanisms that
underlie both in vivo associations and in vitro phenotypes. Our NIGMS-supported preliminary data show that
there are four common species of nasal Corynebacterium. Three of these are positively correlated with D. pigrum
and enhance D. pigrum growth in vitro. Furthermore, cocultivation of D. pigrum with Corynebacterium
pseudodiphtheriticum together robustly inhibits S. pneumoniae in vitro, compared to either alone. D. pigrum also
inhibits S. aureus growth in vitro. These in vitro results support a role for in vivo interactions with potential health
benefits. To understand microbe-microbe and microbe-epithelium interactions in the human nasal passages, we
will use human nasal epithelial organoids at an air-liquid interface (aka nasanoids) as an innovative biomimetic
model system in collaboration with our Organoid Core. Microbial communities are characterized by a network of
metabolic interactions among microbes and with the environment. Genomic analysis uncovered D. pigrum
auxotrophies indicating it depends on the host or microbial neighbors for key nutrients. Our research will address
gaps in understanding the food web that supports human nasal microbiota; the effects on the epithelium of
hosting microbes; and the physiology and function of potentially beneficial nasal bacteria. A key advantage of
using human nasal microbiota to identify metabolic interactions is that it is a self-contained bacterial-epithelial
system with regard to nutrients. We will use complementary approaches including pan-genomics, metabolic
modeling, dual bacteria-epithelium transcriptomics, metabolomics and genetic engineering. We will also tackle
key technical challenges in the nasal microbiome field to facilitate identification of metabolites, proteins and
genes involved in interactions. To advance research on D. pigrum and nasal Corynebacterium, we have
established a large culture collection of nasal bact...

## Key facts

- **NIH application ID:** 10378695
- **Project number:** 5R35GM141806-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Katherine Paige Lemon
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378695

## Citation

> US National Institutes of Health, RePORTER application 10378695, Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota (5R35GM141806-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10378695. Licensed CC0.

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