Comparative pathogenomics of Clostridium tetani

Area of Science:

• Microbiology
• Genomics
• Bacterial Pathogenesis

Background:

• Clostridium tetani and Clostridium botulinum produce potent neurotoxins.
• Research on C. tetani genetics is less extensive than for C. botulinum due to perceived lower genetic diversity and reduced public health threat from tetanus.
• Genomic data on the U.S. vaccine strain of C. tetani is needed to understand its genetic relationship to European vaccine strains.

Purpose of the Study:

• To acquire genomic data on the U.S. vaccine strain of C. tetani.
• To compare genomic data of U.S. vaccine strains with European vaccine and wild-type strains.
• To investigate the genetic relationship and mobile genome diversity within C. tetani.

Main Methods:

• High-throughput genomic sequencing of two wild-type and two vaccine C. tetani strains.
• Comparative genomic analysis including single nucleotide polymorphisms (SNPs).
• Analysis of mobile genome elements: flagellar glycosylation island, bacteriophage insertion regions, CRISPR-Cas systems, and plasmids.

Main Results:

• Vaccine strains formed a distinct clade compared to wild-type strains based on mobile element variations.
• CRISPR-Cas systems (Type IA, IB, IIIA) were analyzed, with intact Type IA and IB systems found in most strains.
• Phage infection histories inferred from CRISPR-Cas sequences suggest C. tetani interacts with common environmental phages.

Conclusions:

• Genomic variations in mobile elements differentiate vaccine and wild-type C. tetani strains.
• Phylogenetic histories from SNPs, mobile elements, and CRISPR-Cas systems suggest a common ancestor for vaccine and wild-type strains.
• The findings provide insights into the genetic diversity and evolution of C. tetani, particularly concerning vaccine strains.