The Ravel Laboratory for Microbial Genomics
Whole genome sequencing of pathogenic Bacillus cereus isolates
Collaborators: David Rasko, University of Texas Southwestern Medical Center, Dallas, TX. Alex Hoffmaster, CDC; Anne-Brit Kolstø and Ole Andreas Høkstad, University of Olso, Norway.
Funding: NIAID – Microbial Sequencing Center.
Through whole genome sequencing, we are expanding the understanding of the pathogenicity of the Bacillus cereus group of organisms, by sequencing and annotating the genomes of 10 strains, encompassing the breadth of diversity that has been shown in this medically important and understudied group of organisms. Pathogenic B. cereus spp. are emerging and established pathogens of immediate biomedical, public health and biodefense/biopreparedness concerns.
As a category B agent, B. cereus causes a wide range of clinical infections that fall into six broad groups among which the proposal focuses on the most acute forms: (1) respiratory infections; (2) soft tissue infections such as endophthalmitis; and (3) food poisoning, characterized by toxin-induced emetic and diarrheagenic syndromes. The incidence of reported non-food poisoning-related infections is likely to increase because of greater recognition of B. cereus as a pathogen outside the gut and respiratory tract. These infections include but are not limited to: (1) bacteremia and septicimia, (2) central nervous system infections, including meningitis, abscesses and shunt-associated infections, (3) other local infections, particularly of burns, traumatic or post-surgical wounds.
Respiratory infections
B. cereus respiratory infections involving both the lung and pleural space are still reported unfrequently, because they are often misdiagnosed, however, they are potentially life-threatening. Complications can be severe, and in some cases lethal. Reported cases of pneumonia were associated with clinical presentations such as massive hemoptysis, acute respiratory failure, tension pneumothorax, empyema or bronchopleural fistula. The discovery of an increasing number of B. cereus isolates with pathogenicity resembling that of B. anthracis, the causative agent of anthrax, emphasizes the challenges that public health professional are facing. To achieve maximal biopreparedness, they must be able to quickly recognize clearly identified select agents, a task that has proven to be extremely difficult with our current understanding of this group of organisms. Additional genome sequences for this group of organisms will be extremely valuable in identifying novel virulence factors that are critical to anthrax-like pathogenicity.
Diarrheal and Emetic Syndromes
B. cereus is the etiological agent of two important clinical food-borne poisoning syndromes that are characterized by diarrhea and abdominal pain (diarrheal syndrome) or by nausea and vomiting (emetic syndrome), respectively. Confirmed outbreaks in the United States date from the end of the 1960s. Since then there have been several outbreaks in which among other foods, rice, meat products, sprouts, mashed potatoes, beef stew, and apples were implicated. The diarrheal syndrome resembles Clostridium perfringens food poisoning and is due to the effects of an enterotoxin that is immunologically unrelated to the C. perfringens enterotoxin. The enterotoxin may be preformed in the food or may be produced within the small intestine. Patients experience profuse diarrhea with abdominal pain and cramps, but only rarely vomiting or fever.
The emetic syndrome is caused by the emetic toxin, or vomiting factor, a small peptide that is highly thermostable and resistant to proteolytic cleavage. The emetic syndrome is often characterized by the ingestion of rice- and pasta-based food and a short incubation period of 1h to 5h, during which the emetic toxin induces nausea, vomiting, abdominal cramps, and also diarrhea in about one third of patients. The symptomatology and incubation period resembles that of Staphylococcus aureus.
While they cause the majority of the medical cases attributed to B. cereus, no emetic or diarrheal B. cereus strains have been sequenced to date.
For a complete list of organisms and update on the project, click here
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