PERK Pathway Inhibitors Cure Group A Streptococcal Necrotizing Fasciitis in a Murine Model

Aparna Anand, Abhinay Sharma, Miriam Ravins, Atul Kumar Johri, Boaz Tirosh, Emanuel Hanski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Group A streptococcus (GAS) is a Gram-positive human pathogen that causes invasive infections with mild to life-threatening severity, like toxic shock syndrome, rheumatic heart disease, and necrotizing fasciitis (NF). NF is characterized by a clinical presentation of widespread tissue destruction due to the rapid spread of GAS infection into fascial planes. Despite quick medical interventions, mortality from NF is high. The early onset of the disease is difficult to diagnose because of non-specific clinical symptoms. Moreover, the unavailability of an effective vaccine against GAS warrants a genuine need for alternative treatments against GAS NF. One endoplasmic reticulum stress signaling pathway (PERK pathway) gets triggered in the host upon GAS infection. Bacteria utilize asparagine release as an output of this pathway for its pathogenesis. We reported that the combination of sub-cutaneous (SC) and intraperitoneal (IP) administration of PERK pathway inhibitors (GSK2656157 and ISRIB) cures local as well as systemic GAS infection in a NF murine model, by reducing asparagine release at the infection site. This protocol's methodology is detailed below.

Original languageAmerican English
Article numberexxxx
JournalBio-protocol
Volume12
Issue number24
DOIs
StatePublished - 20 Dec 2022

Bibliographical note

Publisher Copyright:
Copyright: © 2022 The Authors.

Keywords

  • Endoplasmic reticulum stress
  • GSK2656157
  • Group A streptococcus
  • ISRIB
  • Necrotizing fasciitis murine model
  • PERK pathway

Fingerprint

Dive into the research topics of 'PERK Pathway Inhibitors Cure Group A Streptococcal Necrotizing Fasciitis in a Murine Model'. Together they form a unique fingerprint.

Cite this