Bacillus cereus Database
A key member of the Bacillus cereus group, Bacillus anthracis is defined by phenotypic and molecular characteristics that are conferred by two large plasmids, pXO1 and pXO2. However the very concept of B. anthracis as a distinct species has been called into question by recent discoveries of "intermediate" isolates identified as B. cereus and B. thuringiensis but possessing features similar to those of B. anthracis, including large plasmids that share a common backbone with pXO1 and/or pXO2. Many of these "intermediate" isolates possess potential or demonstrated lethal pathogenic properties and are sometimes called "anthrax-like", even though they do not meet the strict definition of anthrax-causing B. anthracis. We recently showed that pXO1- and pXO2-like plasmids are widely prevalent in environmental isolates of the B. cereus group.
Because B. anthracis-like isolates do not possess all the molecular hallmarks of typical B. anthracis, there is a significant risk that they would escape being flagged as dangerous. Consequently, accidental infection by naturally occurring pathotypes which are not immediately recognized as life-threatening could present a serious health concern. Such cases have already been reported, some with a fatal outcome. The second risk posed by these B. anthracis-like isolates could be the intentional use as "stealth anthrax" bioweapon, either in natural form or with genetic modifications that would require only minimal skills and facilities to produce. To address these risks, this proposal focuses on three main questions:
- What is the functional repertoire of the pXO1- and pXO2-like plasmids and does it include known virulence-related genes?
- Are pXO1-like and/or pXO2-like plasmids associated with chromosomal genetic features that indicate pathogenic potential and/or similarity with known B. anthracis-like strains of B. cereus?
- How does the genomic diversity within this collection of potentially B. anthracis-like strains strains compare to other available B. cereus group genomes?
This emerging picture of a virulence-associated plasmid gene pool highlights the inadequacy of the classical B. cereus species definitions, at least for operational biosafety purposes. However, the observation that pXO1- and/or pXO2-like plasmids seem to be systematically present in the dangerous pathotypes of the B. cereus group provides a valuable starting point to investigate the extent to which such strains occur naturally in the environment.
Here we propose to sequence a panel of 96 isolates representing a variety of plasmid contents and environmental origins to achieve three specific outcomes:
- Assess the potential for accidental infections;
- Assess the theoretical feasibility of bioweapons development from naturally occurring bacterial isolates;
- Generate sequence data suitable for the development of improved diagnostics and clinical countermeasures by specialists in the community.
This sequencing project was supported by the National Institute of Allergy and Infectious Disease, National Institutes of Health funded Genome Sequencing Center for Infectious Diseases at the Broad Institute.