Group A Streptococcus host-pathogen dual crosstalk
Abhinay Sharma1, Usha Kantiwal1, Aparna Anand1
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.
Trends in Microbiology
|April 9, 2026
Summary
Group A Streptococcus exploits the host unfolded protein response (UPR) to increase asparagine (Asn) production. This bacterial manipulation enhances pathogen growth and virulence by hijacking a key metabolic pathway.
Area of Science:
- Microbiology
- Cellular Biology
- Host-Pathogen Interactions
Background:
- The unfolded protein response (UPR) is a critical cellular stress pathway.
- Microbial manipulation of the UPR is increasingly recognized, but bacterial exploitation, especially by extracellular pathogens, is less understood.
- Group A Streptococcus (GAS) is a significant human pathogen causing diverse diseases.
Purpose of the Study:
- To investigate how the bacterial pathogen Group A Streptococcus (GAS) exploits the host unfolded protein response (UPR).
- To elucidate the specific UPR arm and metabolic pathways involved in GAS pathogenesis.
- To establish a link between host ER stress and GAS virulence.
Main Methods:
- Selective activation of the PERK-eIF2α-ATF4 arm of the UPR by GAS.
- Induction of host asparagine (Asn) biosynthesis.
- Import of host-derived Asn by GAS for metabolic activity and growth.
Main Results:
- GAS selectively activates the PERK-eIF2α-ATF4 pathway of the UPR.
- This activation drives host asparagine (Asn) biosynthesis.
- GAS imports Asn to enhance its metabolic activity, growth, and virulence, creating a direct link between ER stress and pathogenicity.
- The Asn-driven circuit parallels mechanisms in cancer biology.
Conclusions:
- Group A Streptococcus manipulates the host UPR to enhance its own virulence.
- Asparagine (Asn) serves as a critical metabolic signal linking host ER stress to GAS pathogenicity.
- This study reveals a novel metabolic strategy employed by bacteria to exploit host cellular machinery.
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