Bacillus Cereus - Pathogenesis

Pathogenesis

B. cereus is responsible for a minority of foodborne illnesses (2–5%), causing severe nausea, vomiting and diarrhea. Bacillus foodborne illnesses occur due to survival of the bacterial endospores when food is improperly cooked. Cooking temperatures less than or equal to 100 °C (212 °F) allows some B. cereus spores to survive. This problem is compounded when food is then improperly refrigerated, allowing the endospores to germinate. Cooked foods not meant for either immediate consumption or rapid cooling and refrigeration should be kept at temperatures above 60 °C (140 °F). Germination and growth generally occurs between 10–50 °C (50–122 °F), though some strains are psychrotrophic. Bacterial growth results in production of enterotoxins, one of which is highly resistant to heat and to pH between 2 and 11; ingestion leads to two types of illness, diarrheal and emetic (vomiting) syndrome.

• The diarrheal type is associated with a wide-range of foods, has an 8- to 16.5-hour incubation time and is associated with diarrhea and gastrointestinal pain. Also known as the long-incubation form of B. cereus food poisoning, it might be difficult to differentiate from poisoning caused by Clostridium perfringens.
• The emetic form is commonly caused by rice that is not cooked for a time and temperature sufficient to kill any spores present, then improperly refrigerated. It can produce a toxin, cereulide, which is not inactivated by later reheating. This form leads to nausea and vomiting 1–5 hours after consumption. It can be difficult to distinguish from other short-term bacterial foodborne pathogens such as Staphylococcus aureus.

The diarrhetic syndromes observed in patients are thought to stem from the three toxins Hemolysin BL Hbl, Nonhemolytic Enterotoxin Nhe and Cytotoxin K CytK. The nhe/hbl/cytK genes are located on the chromosome of the bacteria. Transcription of these genes is controlled by PlcR. These genes occur as well in the toxonomically related B. thuringensis and B. anthracis. These enterotoxins are all produced in the small intestine of the host, thus thwarting the issue of digestion by host endogenous enzymes. The Hbl and Nhe toxins are pore-forming toxins closely related to ClyA of E. coli. The proteins exhibit a conformation known as "beta-barrel" that can insert into cellular membranes due to a hydrophobic exterior, thus creating pores with hydrophilic interiors. The effect is loss of cellular membrane potential and eventually cell death. CytK is a pore-forming protein more related to other hemolysins.

It was previously thought that the timing of the toxin production might be responsible for the two different courses of disease, but in fact the emetic syndrome is caused by a toxin called cereulide that is found only in emetic strains and is not part of the "standard toolbox" of B. cereus. Cereulide is cyclic polypeptide containing 3 repeats of 4 amino acids: D-Oxy-Le—D-Ala—L-Oxy-Val—L-Va (similar to Valinomycin produced by Streptomyces griseus) produced by nonribosomal peptide synthesis (NRPS). Cereulide is believed to bind to 5-hydroxytryptamine 3 (5-HT3) serotonin receptors activating them and leading to increased afferent vagus nerve stimulation. It was shown independently by two research groups to be encoded on multiple plasmids: pCERE01 or pBCE4810. Plasmid pBCE4810 shares homology with the Bacillus anthracis virulence plasmid pXO1, which encodes the anthrax toxin. Periodontal isolates of B. cereus also possess distinct pXO1-like plasmids. Like most of cyclic peptides containing nonproteinogenic amino acids, cereulid is resistant to heath, proteolyis and acid conditions.

B. cereus is also known to cause chronic skin infections that are difficult to eradicate though less aggressive than necrotizing fasciitis. B. cereus can also cause keratitis. It mentioned as pathogenic microflora in pharmaceutical oral products in Brazilian Phamacopaeia.