# Functional analysis of a Group A streptococcal locus important for fitness in soft tissue

> **NIH NIH F31** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $20,968

## Abstract

PROJECT SUMMARY
A pathogen’s ability to adapt to different environments is an important factor in its survival, infection,
and persistence within its host. As a strict human pathogen, Streptococcus pyogenes (Group A
Streptococcus, GAS) causes over 500,000 deaths annually. Even though it commonly manifests as
superficial infections (e.g. strep throat), GAS also causes life-threatening diseases (e.g. necrotizing
fasciitis, toxic shock syndrome) when it invades normally sterile tissues from initial sites of infection. It
is imperative to gain a better understanding of GAS pathophysiology and the genetic requirements it
needs to infect varying host environments. Our lab performed an in vivo transposon sequencing (Tn-seq)
screen in a clinically relevant M1T1 5448 GAS strain to define the genetic requirements needed for GAS
fitness in the subepithelial tissue, where we found a previously uncharacterized locus (scfCDE) to be
essential for this environment. Based on homology alone, scfCDE are predicted to encode for a putative
ABC importer. Because the locus has not been experimentally examined before, this proposal will explore
the functional roles of scfCDE in GAS cellular pathways and virulence, hypothesizing that scfCDE encode
membrane-associated proteins that play integral roles in GAS fitness in host tissue, importing a substrate
into the cell important for GAS pathophysiology. This study will examine the scfCDE locus for
phenotypes in nutrient utilization and in stress-induced environments to identify potential substrates
these proteins may transport, explore its genetic architecture, expression, and regulation of the operon,
and lastly, explore whether scfCDE are important for colonization, growth in human blood, and innate
immune evasion using established in vivo and ex vivo models of GAS infection. Since scfCDE are
conserved in GAS and other Firmicutes, successful completion of this project will potentially contribute
to the development of novel therapeutic strategies against GAS and other important Gram+ pathogens.

## Key facts

- **NIH application ID:** 10089390
- **Project number:** 5F31AI140592-03
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Rezia Era Braza
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $20,968
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089390

## Citation

> US National Institutes of Health, RePORTER application 10089390, Functional analysis of a Group A streptococcal locus important for fitness in soft tissue (5F31AI140592-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10089390. Licensed CC0.

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