TY  - JOUR
TI  - PERK Pathway Inhibitors Cure Group A Streptococcal Necrotizing Fasciitis in a Murine Model
AU  - Anand, Aparna 
AU  - Sharma, Abhinay  
AU  - Ravins, Miriam  
AU  - Johri, Atul Kumar
AU  - Tirosh, Boaz 
AU  - Hanski, Emanuel 
VL  - 12
IS  - 24
PY  - 2022
DA  - 2022/12/20
SP  - e4589
C1  - Bio-protocol 2022;12:e4589
DO  - 10.21769/BioProtoc.4589
UR  - https://doi.org/10.21769/BioProtoc.4589
AB  - 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.
KW  - Group A streptococcus
KW  - Necrotizing fasciitis murine model
KW  - Endoplasmic reticulum stress
KW  - PERK pathway
KW  - GSK2656157
KW  - ISRIB
JF  - Bio-protocol
SN  - 2331-8325
PB  - Bio-protocol LLC.
BIO101  - False