# Contribution of LiaFSR to pathogenesis and carriage of group A Streptococcus

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $385,000

## Abstract

Contribution of LiaFSR to pathogenesis and carriage of group A Streptococcus
PROJECT SUMMARY
Asymptomatic carriage of bacterial pathogens is a common but poorly understood phenomenon. Group A
Streptococcus (GAS) is the cause of severe infections such as the “flesh-eating” necrotizing fasciitis and more
benign infections like pharyngitis. However, GAS is also carried in the throats of humans in the absence of
symptoms (i.e. asymptomatic carriage). We understand little of the bacterial molecular genetic determinants
contributing to GAS carriage. We hypothesize that mutations in GAS carrier strains contribute to a unique
phenotype characterized by increased ability to adhere to mucosal surfaces and decreased ability to cause
disease. We identified a mutation, unique to a GAS carrier strain, leading to a single amino acid change in a
highly conserved sensor kinase, LiaS, of the poorly described GAS regulatory three component system (3CS)
LiaFSR. We previously showed complete recapitulation of the carrier phenotype (increased adherence to
mucosal surfaces and decreased virulence) when the carrier mutation in liaS was introduced into a serotype-
matched disease-causing strain of GAS. We also discovered that the carrier mutation altered global gene
regulation. The LiaFSR 3CS has been described in other bacteria but its contribution to virulence gene
regulation in pathogenic bacteria is largely unknown. Further, the mechanism by which the carrier amino acid
change in LiaS leads to gene dysregulation and the carrier phenotype is incomplete. We hypothesize that the
carrier mutation alters function of the sensor kinase, LiaS, resulting in decreased activation of the target
response regulator, LiaR, affecting gene regulation and leading to the carrier phenotype. By defining the
mechanism by which the carrier mutation alters gene regulation and leads to a carrier phenotype, we may
better understand the gene regulatory events associated with the transition from disease to carriage in GAS.
We have proposed three aims to test our hypothesis. In Aim 1, we will define in vitro and ex vivo-human
conditions that activate the LiaFSR system. Aim 2 will determine global gene regulation by LiaFSR in GAS
and define the genes affected by the carrier LiaS mutation. In Aim 3, we will demonstrate the effect of the
carrier mutation on the function of LiaS and subsequent response regulator activation. Upon completion of
these aims, we will have defined the mechanism by which the carrier mutation leads to gene dysregulation and
the carrier phenotype and simultaneously learned more about gene regulation in GAS pathogenesis.
Ultimately, these studies will provide a foundation for future carriage research and potentially have implications
in diagnostic, therapeutic, and vaccine development for GAS and other bacterial pathogens.

## Key facts

- **NIH application ID:** 9837406
- **Project number:** 5R01AI125216-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Anthony Richard Flores
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2017-01-16 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837406

## Citation

> US National Institutes of Health, RePORTER application 9837406, Contribution of LiaFSR to pathogenesis and carriage of group A Streptococcus (5R01AI125216-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9837406. Licensed CC0.

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