# The impact of gestational diabetes on Group B Streptococcal virulence and host immune response

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2024 · $198,614

## Abstract

PROJECT SUMMARY
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
neonatal morbidity and mortality, yet the factors driving GBS ascension into the uterus are poorly defined. The
current standard of care, antibiotic prophylaxis to GBS-positive mothers, is insufficient to prevent GBS-
associated preterm births of stillbirths and exposes ~1 million U.S. infants to antibiotics each year. Understanding
the biological principles controlling GBS-host dynamics is critical to developing defined, long-lasting preventions
for GBS infections in pregnancy and the early neonatal period. Clinical studies have identified gestational
diabetes mellitus (GDM) as a key risk factor for maternal colonization and neonatal disease. The objective of
this proposal is to interrogate the contribution of maternal immunity and GBS transcriptional adaptions in the
propagation of GDM-associated invasive GBS disease and adverse birth outcomes. Our preliminary murine
studies show enhanced susceptibility of diabetic mice to GBS fetal dissemination and adverse outcomes, altered
cytokine profiles, and differential GBS gene expression in a novel murine GDM model. We hypothesize that
GDM renders the host more susceptible to GBS by perturbing maternal immunity and altering GBS transcription
to enhance virulence and fitness. This hypothesis will be interrogated through specific aims designed to
determine: 1) the impact of GDM on the maternal and fetal immune responses at baseline and during GBS
ascending infection, and 2) the transcriptional adaptions required for GBS pathogenesis in the pregnant host in
the presence or absence of GDM. These aims are advanced using multiple innovative tools including recently
established murine models of GDM and GBS vaginal colonization, immune profiling across maternal and fetal
tissues, and comparative GBS transcriptional analyses from commensal and invasive niches. This research
takes place in the dynamic and interdisciplinary environment of Baylor College of Medicine and the Texas
Medical Center with diverse expertise in GBS-host interactions of the female reproductive tract, employment of
animal models to study gestational diabetes mellitus, and genetics of Streptococcal pathogenesis. This research
strategy seeks to more fully understand the complex processes governing host and pathogen dynamics in the
context of pregnancy and maternal metabolic disease. These studies will launch mechanistic studies into key
pathways dictating pregnancy outcomes, and will inform new therapeutic strategies for detecting and preventing
GBS infections in both healthy women and those with gestational diabetes.

## Key facts

- **NIH application ID:** 10873328
- **Project number:** 5R21AI173448-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Katy Patras
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $198,614
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873328

## Citation

> US National Institutes of Health, RePORTER application 10873328, The impact of gestational diabetes on Group B Streptococcal virulence and host immune response (5R21AI173448-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10873328. Licensed CC0.

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