Bacillus cereus: Epidemiology, Virulence Factors, and Host-Pathogen Interactions

Abstract

Bacillus cereus is an important human pathogen, and new findings have expanded our understanding of how this bacterium causes disease. B. cereus Hemolysin BL (HBL) and nonhemolytic enterotoxin (NHE) induce membrane pore formation, leading to activation of the NLRP3 inflammasome, systemic inflammation, and death. Lipopolysaccharide-induced tumor necrosis factor (TNF)-α factor (LITAF) and cell death-inducing P53 target 1 (CDIP1) are bona fide mammalian surface receptors of HBL. These newly identified toxin receptors and the NLRP3 inflammasome represent unique targets for potential future therapies against severe B. cereus infections. The toxin-producing bacterium Bacillus cereus is an important and neglected human pathogen and a common cause of food poisoning. Several toxins have been implicated in disease, including the pore-forming toxins hemolysin BL (HBL) and nonhemolytic enterotoxin (NHE). Recent work revealed that HBL binds to the mammalian surface receptors LITAF and CDIP1 and that both HBL and NHE induce potassium efflux and activate the NLRP3 inflammasome, leading to pyroptosis. These mammalian receptors, in part, contribute to inflammation and pathology. Other putative virulence factors of B. cereus include cytotoxin K, cereulide, metalloproteases, sphingomyelinase, and phospholipases. In this review, we highlight the latest progress in our understanding of B. cereus biology, epidemiology, and pathogenesis, and discuss potential new directions for research in this field.