# Polymicrobial Interactions that Facilitate Mucosal Colonization by Group B Streptococcus

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2024 · $234,000

## Abstract

PROJECT SUMMARY
Commensal
pathogenic Group B Streptococcus (GBS) is a Gram-positive pathobiont that asymptomatically
colonizes mucosal sites including the gastrointestinal tract and the female reproductive tract (FRT), however
microorganisms contribute significantly to the mucosal environment and host defense against
 bacteria. 
(GI)
the interactions with GBS and native microbes in these niches is largely unstudied. During pregnancy GBS
vaginal colonization and ascending infection is associated with adverse pregnancy outcomes and fetal/neonatal
infection. The
to
establishment of GBS intestinal colonization in newborns i s also believed to be a critical precursor
 Late-Onset Disease (LOD) which typically presents as meningitis and results in long-term neurological
sequalae in survivors. The bacterial and host determinants that promote GBS mucosal colonization and systemic
infection, as well as the role of native microbiota are essentially unknown and represent significant knowledge
gaps in the field. Previous microbiome studies have demonstrated that GBS colonization impacts vaginal
microbial diversity. Using a mouse model of GBS vaginal colonization, we found that GBS vaginal persistence
is associated with the presence of Akkermansia muciniphila (AM), a Gram-negative intestinal commensal that
degrades mucin; however, the specific mechanism(s) for this synergy is unknown. Our preliminary data show
that the presence of AM dramatically increases GBS adherence to human vaginal epithelial cells (hVEC). Using
triple RNA-sequencing we identified numerous GBS and hVEC genes that are significantly altered in the
presence of AM, including increased bacterial surface adhesins, such as pili, and decreased transcription of
hVEC genes involved in neutrophil signaling and chemotaxis. I hypothesize that AM may promote the observed
increase in GBS vaginal persistence by increasing GBS attachment and modulating host immune responses
that dampen host defense against GBS. I further hypothesize that AM will similarly promote GBS intestinal
colonization which could impact LOD. To examine these hypotheses, we propose the following aims: 1)
Determine the mechanism by which AM promotes GBS attachment to epithelium, 2) Characterize the impact of
AM on mucosal immunity in the FRT, and 3) Examine the effect of AM on GBS intestinal
These
mucosal
colonization and LOD.
 studies will greatly increase our knowledge of GBS – commensal interactions which may impact GBS
colonization and neonatal disease.

## Key facts

- **NIH application ID:** 10996581
- **Project number:** 1R21AI186346-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kelly S Doran
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2024-06-26 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996581

## Citation

> US National Institutes of Health, RePORTER application 10996581, Polymicrobial Interactions that Facilitate Mucosal Colonization by Group B Streptococcus (1R21AI186346-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10996581. Licensed CC0.

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