Genomics of Clostridium tetani

Abstract

Genomic information about Clostridium tetani, the causative agent of the tetanus disease, is scarce. The genome of strain E88, a strain used in vaccine production, was sequenced about 10 years ago. One additional genome (strain 12124569) has recently been released. Here we report three new genomes of C. tetani and describe major differences among all five C. tetani genomes. They all harbor tetanus-toxin-encoding plasmids that contain highly conserved genes for TeNT (tetanus toxin), TetR (transcriptional regulator of TeNT) and ColT (collagenase), but substantially differ in other plasmid regions. The chromosomes share a large core genome that contains about 85% of all genes of a given chromosome. The non-core chromosome comprises mainly prophage-like genomic regions and genes encoding environmental interaction and defense functions (e.g. surface proteins, restriction-modification systems, toxin-antitoxin systems, CRISPR/Cas systems) and other fitness functions (e.g. transport systems, metabolic activities). This new genome information will help to assess the level of genome plasticity of the species C. tetani and provide the basis for detailed comparative studies.

The role of the single interchains disulfide bond in tetanus and botulinum neurotoxins and the development of antitetanus and antibotulism drugs

“…TeNT is always mentioned and discussed as a single toxin, at variance from the many BoNTs. But this is no longer appropriate as novel TeNT isoforms with slight, but significant, amino acid sequence changes are reported (Alam, Dixit, Tomar, & Singh, ; Bruggemann et al, ; Cohen, Wang, Shen, Wu, & Keller, ; Dixit, Alam, & Singh, ), and surely many more will be found as the sequence of more C. tetani TeNT encoding plasmids become available.…”

Mobile genetic elements and pathogenicity islands encoding bacterial toxins

“…This study also suggested that stx expression, and thus virulence, may correlate with the genetic structure of the stx sequence context and the presence of a particular Q antiterminator protein variant [293]. Comparative genomewide analysis, including protein toxin-encoding mobile elements, has been performed in order to gain insights into microepidemiology and evolution of toxin variants [95,99,264,265,[294][295][296].…”

“…The Clostridium tetani structural gene tent encoding the tetanus neurotoxin (TeNT) is located on a 74-kb plasmid such as pE88 [93][94][95][96]. Five tetanus toxin-encoding plasmids have been sequenced.…”

“…Five tetanus toxin-encoding plasmids have been sequenced. Whereas they may differ with regard to their gene content, the tent sequences located on these plasmids are highly conserved [95].…”

From saprophytic to toxigenic clostridia, a complex evolution based on multiple diverse genetic transfers and/or rearrangements

“…BoNTs have sustained numerous genetic rearrangements (mutations, duplication, recombination), resulting in multiple BoNT types and subtypes, whereas only a unique TeNT sequence has been reported until now. Similarly, the genome background of BoNT-producing clostridia is extremely diverse, and only restricted genetic diversity is observed in C. tetani strains (see [5,6,20,21]).…”