Cereulide synthetase gene cluster from emetic Bacillus cereus: Structure and location on a mega virulence plasmid related to Bacillus anthracis toxin plasmid pXO1
Open Access
- 2 March 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Microbiology
- Vol. 6 (1), 20
- https://doi.org/10.1186/1471-2180-6-20
Abstract
Cereulide, a depsipeptide structurally related to valinomycin, is responsible for the emetic type of gastrointestinal disease caused by Bacillus cereus. Recently, it has been shown that this toxin is produced by a nonribosomal peptide synthetase (NRPS), but its exact genetic organization and biochemical synthesis is unknown. The complete sequence of the cereulide synthetase (ces) gene cluster, which encodes the enzymatic machinery required for the biosynthesis of cereulide, was dissected. The 24 kb ces gene cluster comprises 7 CDSs and includes, besides the typical NRPS genes like a phosphopantetheinyl transferase and two CDSs encoding enzyme modules for the activation and incorporation of monomers in the growing peptide chain, a CDS encoding a putative hydrolase in the upstream region and an ABC transporter in the downstream part. The enzyme modules responsible for incorporation of the hydroxyl acids showed an unusual structure while the modules responsible for the activation of the amino acids Ala and Val showed the typical domain organization of NRPS. The ces gene locus is flanked by genetic regions with high homology to virulence plasmids of B. cereus, Bacillus thuringiensis and Bacillus anthracis. PFGE and Southern hybridization showed that the ces genes are restricted to emetic B. cereus and indeed located on a 208 kb megaplasmid, which has high similarities to pXO1-like plasmids. The ces gene cluster that is located on a pXO1-like virulence plasmid represents, beside the insecticidal and the anthrax toxins, a third type of B. cereus group toxins encoded on megaplasmids. The ces genes are restricted to emetic toxin producers, but pXO1-like plasmids are also present in emetic-like strains. These data might indicate the presence of an ancient plasmid in B. cereus which has acquired different virulence genes over time. Due to the unusual structure of the hydroxyl acid incorporating enzyme modules of Ces, substantial biochemical efforts will be required to dissect the complete biochemical pathway of cereulide synthesis.Keywords
This publication has 52 references indexed in Scilit:
- Unusual Group II Introns in Bacteria of theBacillus cereusGroupJournal of Bacteriology, 2005
- Genomics of the group of organismsFEMS Microbiology Reviews, 2005
- Molecular Mechanisms Underlying Nonribosomal Peptide Synthesis: Approaches to New AntibioticsChemical Reviews, 2005
- Search for Potential Vaccine Candidate Open Reading Frames in theBacillus anthracisVirulence Plasmid pXO1: In Silico and In Vitro ScreeningInfection and Immunity, 2002
- AnthraxAnnual Review of Microbiology, 2001
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- A novel dodecadepsipeptide, cereulide, isolated fromBacillus cereuscauses vacuole formation in HEp-2 cellsFEMS Microbiology Letters, 1994
- Bacillus cereus and its toxinsJournal of Applied Bacteriology, 1994
- Four homologous domains in the primary structure of GrsB are related to domains in a superfamily of adenylate‐forming enzymesMolecular Microbiology, 1992
- Basic local alignment search toolJournal of Molecular Biology, 1990