# Genome-wide assessment of Group B Streptococcus fitness and virulence

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $241,441

## Abstract

Project Summary/Abstract
Streptococcus agalactiae (group B Streptococcus; GBS) is the most common infectious cause of neonatal
morbidity and mortality in the United States and a major global contributor to stillbirth and infection in the
newborn period. While asymptomatic genitorectal GBS colonization is common among healthy adults, vaginal
colonization in late pregnancy is a major risk factor for neonatal infection. For this reason, improved
understanding of bacterial genes that promote vaginal colonization and the transition from a colonizing to an
invasive lifestyle may open avenues to new preventative strategies. Our group has constructed highly
saturated GBS transposon mutant libraries, which have been instrumental in genome-wide assessments of
gene contributions to bacterial fitness in a variety of experimental settings. Recently, we developed a high-
throughput strategy for using these complex, intermixed libraries to generate comprehensive, ordered mutant
libraries of nonessential GBS genes (of which there are approximately 1,700). In Aim 1, we propose to use
techniques and technologies we have developed in order to assemble complete, indexed mutant libraries of
two GBS strains, representing common capsular subtypes recovered from infected patients (serotypes Ia and
V). These indexed libraries—which will be freely shared with the research community at large—will represent a
major advance in pathogenesis research, allowing study of single mutants or curated library sub-pools in a
wide range of experimental designs. In Aim 2, we will use the indexed libraries in a series of studies to fully
characterize the contribution of GBS two-component signaling pathways to vaginal colonization in a mouse
model. Library sub-pools containing knockouts of all 19 GBS two-component systems will be assessed for
constituent mutants with significant fitness defects in the vaginal colonization model. Top candidates will be
validated with targeted isogenic knockout strains, which will also be characterized via RNA-seq to identify
downstream genes regulated by each candidate two-component system. Finally, indexed library knockouts of
each candidate two-component system regulon will be assessed for major fitness contributors in the vaginal
colonization model. These aims will establish new, flexible, and powerful tools for studying GBS pathogenesis.
They will permit unbiased and comprehensive assessment of two-component systems and their regulated
genetic networks as potential targets for preventing neonatal infection.

## Key facts

- **NIH application ID:** 9978309
- **Project number:** 1R21AI147511-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Thomas A Hooven
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $241,441
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978309

## Citation

> US National Institutes of Health, RePORTER application 9978309, Genome-wide assessment of Group B Streptococcus fitness and virulence (1R21AI147511-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9978309. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*