# Nasal Microbial Consortia Combat Antibiotic-Resistant Bacteria

> **NIH NIH U19** · BAYLOR COLLEGE OF MEDICINE · 2024 · $119,807

## Abstract

PROJECT SUMMARY: Project 3
The overall objective and significance of Project 3 is to generate preclinical validation of nasal microbiota-based
therapeutics to block nasal colonization by Staphylococcus aureus and Streptococcus pneumoniae. Our
innovative approach to achieve this is to cultivate human nasal bacteria on human nasal organoids. Together,
S. aureus and S. pneumoniae account for 39% of cases and 29% of deaths attributed to antibiotic-resistant
bacteria in the U.S. Nasal colonization is the primary source of invasive infection by each and the reservoir for
their transmission; blocking colonization reduces both infection and transmission. Lacking effective vaccines
against S. aureus or nonvaccine serotypes of S. pneumoniae, there is an urgent need for new nonantibiotic
approaches to prevent infections by both. Current therapies for nasal decolonization of S. aureus depend on a
topical antibiotic and are temporally correlated with rising antibiotic resistance. Here, we address a gap in
knowledge in how to repopulate with pathobiont-resistant microbiota to improve long-term outcomes. Multiple
nasal microbiota studies report benign bacterial species present when adults are free of S. aureus and when
children are free of S. pneumoniae. For example, nasal colonization by the benign bacterium Dolosigranulum
pigrum, often with harmless Corynebacterium, is associated with the absence of S. pneumoniae in children. In
adults, D. pigrum is inversely associated with S. aureus nasal colonization. Our preliminary data indicate many
strains of D. pigrum inhibit S. aureus growth in vitro. Also, cocultivation of D. pigrum with Corynebacterium
pseudodiphtheriticum robustly inhibits S. pneumoniae growth in vitro, versus either alone. Moreover,
Corynebacterium enhance D. pigrum growth. Thus, our overarching hypothesis is that reproducible consortia of
benign human nasal bacteria can confer colonization resistance to S. aureus and S. pneumoniae, preventing
infection by and transmission of these antibiotic-resistant threats. Moreover, antipathobiont mucosal-active lytic
phage may augment this. Networks of interactions underpin microbiota composition. Relying on consortia avoids
the risk of unexpected community interactions that can occur when adding a single strain and increases the
likelihood of successful repopulation with a desired community. A major hurdle to clinical trials is to identify fully
defined consortia of benign nasal bacterial strains that confer colonization resistance in the context of human
nasal epithelium and promote a healthy, intact epithelial barrier. Our Organoid Cultivation Core has successfully
generated human airway organoids. Thus, we will overcome this hurdle using advances in nasal epithelial
organoids combined with our expertise in cultivating human nasal bacteria and identifying molecular mechanisms
of interactions within nasal microbiota. With methods routinely used by us, Project 1 and the Organoid Cultivation
Core, we will a...

## Key facts

- **NIH application ID:** 11140591
- **Project number:** 3U19AI157981-04S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Katherine Paige Lemon
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $119,807
- **Award type:** 3
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11140591

## Citation

> US National Institutes of Health, RePORTER application 11140591, Nasal Microbial Consortia Combat Antibiotic-Resistant Bacteria (3U19AI157981-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11140591. Licensed CC0.

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