Clostridium botulinum group III: a group with dual identity shaped by plasmids, phages and mobile elements

Abstract

BackgroundClostridium botulinum strains can be divided into four physiological groups that are sufficiently diverged to be considered as separate species. Here we present the first complete genome of a C. botulinum strain from physiological group III, causing animal botulism. We also compare the sequence to three new draft genomes from the same physiological group.ResultsThe 2.77 Mb chromosome was highly conserved between the isolates and also closely related to that of C. novyi. However, the sequence was very different from the human C. botulinum group genomes. Replication-directed translocations were rare and conservation of synteny was high. The largest difference between C. botulinum group III isolates occurred within their surprisingly large plasmidomes and in the pattern of mobile elements insertions. Five plasmids, constituting 13.5% of the total genetic material, were present in the completed genome. Interestingly, the set of plasmids differed compared to other isolates. The largest plasmid, the botulinum-neurotoxin carrying prophage, was conserved at a level similar to that of the chromosome while the medium-sized plasmids seemed to be undergoing faster genetic drift. These plasmids also contained more mobile elements than other replicons. Several toxins and resistance genes were identified, many of which were located on the plasmids.ConclusionsThe completion of the genome of C. botulinum group III has revealed it to be a genome with dual identity. It belongs to the pathogenic species C. botulinum, but as a genotypic species it should also include C. novyi and C. haemolyticum. The genotypic species share a conserved chromosomal core that can be transformed into various pathogenic variants by modulation of the highly plastic plasmidome.

An Atypical Clostridium Strain Related to the Clostridium botulinum Group III Strain Isolated from a Human Blood Culture

“…Interestingly, the housekeeping gene sequences of C. botulinum C strain Eklund clustered within the branch containing C. novyi A, which is distantly related to the one containing the C. botulinum C strain, 468. These results are in agreement with those from the phylogenomic analysis of Skarin et al (16), which show that C. botulinum C strain Eklund is closely related to C. novyi A. The two C. botulinum C strains share 97.2% 16S rRNA gene sequence identity, suggesting that strain Eklund might be assigned to a different species.…”

Horizontal gene transfer of toxin genes inClostridium botulinum

“…15 Two additional draft genomes are also available in GenBank. The main conclusion drawn from analyzing the genome results is that group III strains are more influenced by the plasmids they possess than group I and II strains.…”

“…15 Included among them are elements related to the IS6, IS21, IS256, IS1182 and IS200/ IS605 families. Whereas mobile elements account for 3.4% of the genetic content of the BKT015925 chromosome, the density is highest on the two middle sized plasmids (p2BKT015925 and p3BKT015925) where IS elements constitute 8 and 12% respectively of the total genetic content.…”

Management of Animal Botulism Outbreaks: From Clinical Suspicion to Practical Countermeasures to Prevent or Minimize Outbreaks

“…17 Genes encoding BoNTs can be located on the chromosome or on extrachromosomal elements, such as plasmids or bacteriophages. [18][19][20] Specifically, toxin genes for group III organisms are carried by bacteriophages that exert an unstable lysogenic cycle. Molecular and genomic analysis of the bacteriophage genome revealed that this phage exists as a circular plasmid prophage in the lysogenic state, and it does not integrate into the host chromosome.…”