# Genetic screen to define the regulation of beta-hemolysin toxin expression in Streptococcus agalactiae

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2024 · $229,500

## Abstract

Group B Streptococcus (GBS) is a normal constituent of the intestinal and vaginal flora
in 15–30% of healthy adults. The bacterium can, however, cause infections in elderly and
immunocompromised patients, and pregnant women, and is the main cause of fatal invasive
disease in newborns. GBS translocation through epithelial, endothelial, and placental barriers is
facilitated by a pore-forming toxin β-hemolysin, also known as the β-hemolytic pigmented lipid
or granadaene. To identify factors involved in the regulation of β-hemolysin expression we
developed new peptide-free culture media for screening of a transposon mutant library of GBS
CJB111. The pilot screens identified nine novel genetic loci associated with positive and
negative modulation of β-hemolysin expression. Based on preliminary findings, we hypothesize
that GBS possesses a regulatory mechanism that tailors β-hemolysin expression to the
environment. To unravel the mechanism, we will employ transposon mutant library screening,
RNA-seq and metabolomics analyses, isolation, and de novo sequence determination of
secreted peptide-based repressors. The results of this exploratory work have the potential to
lead to the development of a novel inhibitor of the invasion state of GBS.

## Key facts

- **NIH application ID:** 10844641
- **Project number:** 5R21AI178652-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Natalia Korotkova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,500
- **Award type:** 5
- **Project period:** 2023-05-19 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844641

## Citation

> US National Institutes of Health, RePORTER application 10844641, Genetic screen to define the regulation of beta-hemolysin toxin expression in Streptococcus agalactiae (5R21AI178652-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10844641. Licensed CC0.

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