# Biogenesis and Function of Streptococcus Pyogenes Cell Wall

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2024 · $382,500

## Abstract

Group A streptococcus (GAS, Streptococcus pyogenes) is a leading bacterial pathogen of the
human pharynx and skin. In recent years, a striking resurgence in severe invasive GAS
infections has been observed worldwide. GAS infections account for more than 650,000 cases
of severe invasive disease annually. The invasive GAS infections, necrotizing fasciitis, cellulitis
and erysipelas with concomitant scarlet fever and streptococcal toxic syndrome, are difficult to
treat with antibiotics, and a GAS vaccine is urgently needed to combat this neglected disease. A
major component of the GAS cell wall is the Group A Carbohydrate (GAC) covalently linked to
peptidoglycan, consisting of a polyrhamnose backbone with N-acetylglucosamine (GlcNAc)
side-chains. GAC is an attractive vaccine candidate due to its conserved expression in all GAS
serotypes and the absence of its constitutive component, rhamnose, in humans. Our genetic,
biochemical and structural studies identified two novel modifications of GAC glycans: glycerol
phosphate modification of GAC and de-N-acetylation of the GAC linkage unit. The goal of this
proposal is to characterize the mechanisms of GAC biosynthesis and modification, and
elucidate the roles of cell wall modifications in antimicrobial resistance mechanisms and GAS
pathogenesis. To help answer these questions we will employ a variety of genetic, biochemical,
analytical and structural approaches. The function of cell wall modifications in GAS
pathogenesis will be studied in ex vivo and in vivo models of GAS infection. The proposed
studies provide a platform for design of a safe and effective vaccine against this important
human pathogen and should have broad application to other streptococci which express similar
cell wall polysaccharides. Since the enzymes of the GAC biosynthesis pathway are attractive
drug targets, the proposed studies will have important implications for drug design.

## Key facts

- **NIH application ID:** 10728339
- **Project number:** 5R01AI143690-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Natalia Korotkova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2019-11-25 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10728339

## Citation

> US National Institutes of Health, RePORTER application 10728339, Biogenesis and Function of Streptococcus Pyogenes Cell Wall (5R01AI143690-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10728339. Licensed CC0.

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