The Mechanism for Bacillus cereus Toxicity under Microaerobic Conditions

Abstract

Bacillus cereus, an opportunistic bacterium that causes food poisoning, secretes a multitude of virulence factors that are influenced by environmental stimuli such as oxygen, pH, glucose, and bacterial density. The cytotoxicity of this species has been mainly characterized under aerobic conditions and is primarily attributed to its enterotoxins. This thesis discovers B. cereus and the closely related B. anthracis share a common mechanism of toxicity that exclusively occurs under microaerobic conditions. Toxicity was caused by the permeabilization of the cell membrane by the pore-forming hemolysin cereolysin O (CLO) which facilitated the access of toxic bacterial metabolic product into the cell. This synergistic toxicity appeared to be potentiated by the presence of bovine serum albumin (BSA). Cultures grown in medium containing BSA had an acidification of bacterial supernatants to a pH of 5.2-5.5 indicating albumin increased the generation of anaerobic fermentation products. The activity of CLO and the metabolic product succinic acid were found to be individually inhibited under aerobic conditions. The effect of oxygen availability on B. cereus virulence was strain specific, possibly due to differences in bacterial density influencing the nature and level of enterotoxin production. This thesis highlights a shared mechanism of toxicity in these species through the synergistic effect of their cholesterol-dependent cytolysins and fermentation products.