# Determining the contribution of zinc deficiency to perinatal Group B Streptococcus infections

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $500,207

## Abstract

Project Summary
Zinc deficiency is a global problem associated with preterm birth. Zinc supplementation has also been shown to
prevent preterm birth, but heterogeneous results of clinical studies suggest that certain, as yet undefined,
populations are likely to benefit from zinc more than others. Given the importance of infections as causes of
preterm birth, especially in regions affected by micronutrient deficiency, it is possible that low zinc levels
contribute to the risk for perinatal infections. However, little is known about this possible relationship. Group B
Streptococcus agalactiae (GBS) is a major cause of intrauterine infections during pregnancy, where it can invade
amniotic fluid and infect the developing fetus. The risk for perinatal GBS infections is highest in regions where
micronutrient deficiency is common. To cause intrauterine infection, GBS must first colonize the vagina, where
the low pH stimulates biofilm formation. The vaginal mucosa resists colonization by non-commensal bacteria
through a repertoire of antimicrobial molecules including S100A-family proteins (S100A8/A9 and S100A12) that
participate in nutritional immunity via zinc chelation. Neutrophils also secrete these proteins at sites of bacterial
infection. We have new and exciting data to suggest that zinc deficiency provokes major changes in the behavior
of GBS, with strong effects on the formation of biofilms, structures that aid in bacterial persistence in the
environment, which we speculate are important for vaginal colonization. Furthermore, we have also discovered
that GBS encoded a zinc efflux determinant, CadD, which promotes GBS resistance to zinc intoxication, survival
and persistence within macrophages, and ascending infection in a pregnant host. Given this, we hypothesize
that zinc deficiency, specifically in the context of pregnancy, leads to an increased risk for vaginal GBS
colonization and invasive infection. We will test this by determining the contribution of zinc homeostasis to
bacterial-host interactions, investigating the influence of zinc on immunological responses in human gestational
membranes and disease progression in a mouse model of invasive GBS infection, and evaluate the impact of
zinc homeostasis on GBS colonization in pregnant women. This work will identify novel biomarkers for increased
disease risk and cost-effective dietary or chemotherapeutic strategies that could improve pregnancy outcomes.

## Key facts

- **NIH application ID:** 9930628
- **Project number:** 5R01HD090061-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** David M Aronoff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $500,207
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930628

## Citation

> US National Institutes of Health, RePORTER application 9930628, Determining the contribution of zinc deficiency to perinatal Group B Streptococcus infections (5R01HD090061-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9930628. Licensed CC0.

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