Using More Than 1 (Path)Way to Kill a Host Cell: Lessons From Clostridium perfringens Enterotoxin.

Abstract

Clostridium perfringens enterotoxin (CPE) is responsible for the symptoms of common intestinal infections due to C. perfringens type F isolates. CPE is a pore-forming toxin that uses certain claudins as a receptor. Previous studies showed that, in enterocyte-like Caco-2 cells, low CPE concentrations cause caspase 3-mediated apoptosis but high CPE concentrations cause necrosis. The recent work published in mBio by Shrestha, Mehdizadeh Gohari, and McClane determined that RIP1 and RIP3 are involved in both CPE-mediated apoptosis and necrosis in Caco-2 cells. Furthermore, mixed lineage kinase-domain (MLKL) oligomerization was shown to be important for necrosis caused by CPE, identifying this necrosis as programmed necroptosis. In addition, calpain activation due to Ca2+ influx through the CPE pore was identified as a critical intermediate step for MLKL oligomerization and, thus, CPE-induced necroptosis. These findings may have applicability to understand the action of some other pore-forming toxins that induce necroptosis and may also be important for understanding CPE action in vivo.

• Authors: Bruce McClane, Archana Shrestha
• Journal: Microbiology insights (Microbiol Insights) Vol. 13 Pg. 1178636120931518 ( 2020) ISSN: 1178-6361 [Print] United States
• PMID: 32612365 (Publication Type: Journal Article, Comment)
• Copyright: © The Author(s) 2020.