The genome sequence of Clostridium botulinum type C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny

Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17472-7. doi: 10.1073/pnas.0505503102. Epub 2005 Nov 15.

Abstract

Botulinum neurotoxins (BoNTXs) produced by Clostridium botulinum are among the most poisonous substances known. Of the seven types of BoNTXs, genes for type C1 and D toxins (BoNTX/C1 and D) are carried by bacteriophages. The gene for exoenzyme C3 also resides on these phages. Here, we present the complete genome sequence of c-st, a representative of BoNTX/C1-converting phages. The genome is a linear double-stranded DNA of 185,682 bp with 404-bp terminal direct repeats, the largest known temperate phage genome. We identified 198 potential protein-coding regions, including the genes for production of BoNTX/C1 and exoenzyme C3. Very exceptionally, as a viable bacteriophage, a number of insertion sequences were found on the c-st genome. By analyzing the molecular structure of the c-st genome in lysogens, we also found that it exists as a circular plasmid prophage. These features account for the unstable lysogeny of BoNTX phages, which has historically been called "pseudolysogeny." The PCR scanning analysis of other BoNTX/C1 and D phages based on the c-st sequence further revealed that BoNTX phages comprise a divergent phage family, probably generated by exchanging genomic segments among BoNTX phages and their relatives.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophages / genetics*
  • Base Sequence
  • Blotting, Southern
  • Botulinum Toxins / genetics*
  • Clostridium botulinum / metabolism
  • Clostridium botulinum / virology
  • Genome Components / genetics
  • Genome, Viral*
  • Lysogeny / genetics
  • Lysogeny / physiology*
  • Molecular Sequence Data
  • Open Reading Frames / genetics
  • Sequence Analysis, DNA

Substances

  • Botulinum Toxins
  • botulinum toxin type C

Associated data

  • GENBANK/AB217840
  • GENBANK/AB217841
  • GENBANK/AP008983