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Updated: May 13, 2025

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Group A Streptococcal asparagine metabolism regulates bacterial virulence
Abhinay Sharma1, Aparna Anand1, Miriam Ravins1
1Department of Microbiology and Molecular Genetics, The Institute for Medical Research, Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel.
None:
Group A Streptococcus (GAS) causes various human diseases linked to virulome expression predominantly regulated by the two-component system (TCS), CovR/S. Here, we demonstrate that asparagine (Asn) presence in a minimal chemically defined medium increases virulence gene expression in a CovR-dependent fashion. It also decreases the transcription of asparagine synthetase (AsnA), the ABC transporter responsible for Asn uptake (GlnPQ), and that of the hemolysin toxins responsible for scavenging Asn from the host. Metabolomics data show that Asn availability increases intracellular ADP/ATP ratio, which enhances phosphatase activity in structurally related CovS sensors and is probably responsible for the Asn-mediated decrease in CovR phosphorylation. Mutants deficient in AsnA, GlnPQ, asparaginase, (AsnB) activities are attenuated in a mouse model of human GAS invasive soft tissue infection. The similarity between the mechanisms of Asn-mediated regulation of GAS virulence and tumor growth suggests that, as in cancer, components maintaining Asn homeostasis could be targeted for anti-GAS treatments.
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