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

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. 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. a receptor within the ligand-gated ion channel superfamily. a potentially deadly disease which results in inflammation of the skin, lungs, and gastrointestinal tract. a programmed cell death pathway induced by apoptotic caspases. bacterial infection of the bloodstream. a complex network of cells within the brain’s microvasculature protecting the central nervous system against circulating toxins or pathogens. an emetic toxin produced by B. cereus. a toxin that causes cell death. an oligomeric form of depsipeptide (bicyclic peptide) composed of 12 monomers. the act of vomiting. an infection of the tissue and/or fluid within the eyeball. a microorganism capable of aerobic and anaerobic respiration. apore-forming protein mediating inflammasome-induced cell death known as pyroptosis. an infection caused by toxin-producing bacteria characterized by accumulation of gas within the dead tissue. virulence factors of bacteria that lyse red blood cells. an innate immune signaling complex assembled within the cytoplasm. a compound that facilitates ion transport across a cell membrane. a large plasmid (>100 kb) found as an extrachromosomal genetic element in bacteria. refers to a class of microorganisms that grow well at temperatures between 15 and 45oC. proteases that require metal ions for catalytic activity. a type of mononuclear white blood cell. an inflammasome sensor that responds to a diverse range of stimuli, such as pathogens or endogenous danger signals. receptors of the innate immune system that recognize pathogens or endogenous danger signals. a type of bacterial biofilm that forms at the liquid–air interphase (i.e., floating). flagella projecting from all surfaces of a bacterium. an enzyme that hydrolyzes phospholipids into fatty acids. an enzyme responsible for hydrolyzing lipid phosphatidylinositol and phosphatidylinositol-glycan found on eukaryotic membranes. individual bacteria not attached to one another or to a surface. a toxin which has pore-forming activity and is a key virulence factor of several Gram-positive bacteria. white blood cells with a multilobed nucleus and cytoplasmic granules. an extremophile class of organisms capable of growth below 7oC. an important chemical that acts as a neurotransmitter and a hormone within the body. a protein layer of the cell envelope at the surface of some species of archaea and bacteria. an enzyme responsible for the degradation of sphingomyelin (a eukaryotic membrane sphingolipid). an enzyme capable of catalyzing the dismutation of superoxide radicals to oxygen and hydrogen peroxide. an oligomeric form of depsipeptide (bicyclic peptide) composed of four monomers. a group of membrane-bound innate immune receptors that recognize pathogens and their products to initiate immune responses. one of the 12 cranial nerves that provides autonomic innervation to organs and systems within the body.