# Defining the impact of zinc on Streptococcus agalactiae biofilm and colonization

> **NIH NIH K08** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $28,655

## Abstract

Project Summary
During pregnancy, zinc deficiency is associated with an increased risk of infection. Streptococcus agalactiae,
also known as Group B Streptococcus (GBS), colonizes 20-30% of pregnant women. GBS vaginal colonization
increases the risk for stillbirth, preterm labor, and neonatal sepsis. One strategy that GBS may use to stably
colonize the reproductive tract is to produce biofilm, and we have found that GBS biofilm production is
suppressed in the presence of zinc. This proposal tests the hypothesis that GBS biofilm production is
negatively regulated by zinc, and this biofilm contributes to stable colonization of host tissues by limiting innate
immune responses against GBS. To test this hypothesis, Aim 1 will use mutagenesis and transcriptomic
approaches to identify genetic pathways regulating GBS biofilm. Aim 2 will define the impact of zinc-regulated
biofilm at the host-microbial interface by evaluating GBS mutants lacking cadD, a zinc efflux transporter, which
results in impaired biofilm production. We will examine these interactions using in vitro models of human
vaginal epithelial cells, explanted human fetal membranes, and an Instrumented Fetal Membrane Organ on a
Chip (IFMOC) model under conditions that modify zinc availability. Aim 3 will use a mouse vaginal colonization
model to define how the zinc transporter, cadD, impacts vaginal colonization in settings of zinc deficiency or
supplementation. Completion of these Aims will shed new light on how zinc impacts GBS-host interactions that
culminate in colonization (and infection) of the reproductive tract.
Dr. Ryan Doster is an Instructor in the Division of Infectious Diseases at Vanderbilt University Medical Center.
His past work investigated gestational tissue innate immune responses to infection. This project will expand his
research focus to mechanisms of GBS colonization. This project complements Dr. Doster’s clinical training in
pediatrics and adult infectious diseases medicine. Under the mentorship of Dr. David Aronoff, Dr. Jennifer
Gaddy, and a multidisciplinary Scholarship Oversight Committee, Dr. Doster will master techniques including
bacterial mutagenesis, transcriptomics, and modeling infection within the reproductive tract to determine how
zinc alters bacterial physiology and pathogenesis. Vanderbilt offers cutting-edge technology and expertise in
these areas through Vanderbilt Technologies for Advanced Genomics and other shared research core
facilities. These studies and a strong career development program will prepare Dr. Doster for transition to an
independent researcher investigating the pathogenesis of bacterial infections during pregnancy.

## Key facts

- **NIH application ID:** 10358527
- **Project number:** 5K08AI151100-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Ryan S Doster
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,655
- **Award type:** 5
- **Project period:** 2020-03-09 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358527

## Citation

> US National Institutes of Health, RePORTER application 10358527, Defining the impact of zinc on Streptococcus agalactiae biofilm and colonization (5K08AI151100-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10358527. Licensed CC0.

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