# Characterizing the Impact of Gestational Diabetes on Immunity and Group B Streptococcal Virulence in the Maternal Reproductive Tract

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2022 · $46,752

## Abstract

Infections during pregnancy or the neonatal period account for more than two million deaths globally each year.
Frequently, the pathogens causing these infections begin as residents of the maternal vaginal microbiota and
ascend to the uterus during pregnancy. One such pathogen, group B Streptococcus (GBS), is a leading agent
of neonatal morbidity and mortality with conservative approximations attributing GBS to 147,000 stillbirths and
infant deaths annually. The primary sources of neonatal GBS exposure are thought to be the maternal vaginal
tract during labor and delivery or in utero GBS invasion of placental barriers resulting in fetal infection. Women
with gestational diabetes mellitus (GDM) have a 20-50% increased risk for GBS neonatal sepsis and maternal
invasive disease but mechanistic insight is lacking. While prophylactic antibiotics have decreased the risk of GBS
disease in the first week of life, incidence of GBS-induced stillbirth and preterm birth remains unimproved and
early exposure to antibiotics has long-term health consequences that are yet to be fully elucidated. Thus,
alternative preventative and therapeutic options are urgently needed and can only be achieved by deepening
our understanding of GBS pathogenesis. The aim of this proposal is to determine mechanistic factors that render
gestational diabetic hosts uniquely susceptible to GBS. To do so, I have developed an in vivo model of GBS
ascension in the reproductive tract of gestational diabetic mice. Preliminary data suggests that this model exhibits
increased risk of fetal GBS infection in gestational diabetes as seen in humans. Using this novel model of in
utero GBS dissemination in gestational diabetic mice, I will characterize how gestational diabetes alters GBS
virulence and host immunity in the maternal reproductive tract. I hypothesize that gestational diabetic conditions
perturb host immunity and increase GBS virulence. This hypothesis will be interrogated through specific aims
designed to determine: 1) The impact of gestational diabetes on host immunity and 2) the GBS genes that are
critical for uterine ascension in healthy and gestational diabetic pregnancy. These novel and advanced aims use
multiple innovative tools including a recently established murine model of in utero GBS dissemination in GDM
mice and utilization of mice that harbor a humanized microbiome to explore the role of reproductive tract
microbiota in shaping local immunity against GBS. The breadth of work, mentorship and training plan outlined in
this proposal will equip the candidate with the necessary expertise in mucosal immunology, bioinformatics and
reproductive pathophysiology to achieve independence as a physician-scientist with an exciting career trajectory
in the field of pediatrics. Together, this research proposal seeks to inform novel therapeutic strategies to better
protect maternal-fetal health while advancing our current viewpoint on the complex interplay of gestational
diabetes, immuni...

## Key facts

- **NIH application ID:** 10387379
- **Project number:** 1F31AI167547-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Vicki Mercado
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2021-12-03 → 2025-05-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387379

## Citation

> US National Institutes of Health, RePORTER application 10387379, Characterizing the Impact of Gestational Diabetes on Immunity and Group B Streptococcal Virulence in the Maternal Reproductive Tract (1F31AI167547-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10387379. Licensed CC0.

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