Virulence Mechanisms of Clostridium botulinum A3 on Human Gut

The genome of Clostridium botulinum A3 Loch Maree (4,259,691bp) produces type A3 neurotoxins and other virulence factors, with the bont/A gene on plasmid pCLK_A0076. This strain shows a high evolutionary rate, adapting to hosts and environments, and has 43 unique virulence and host defense genes. Extrachromosomal elements enhance its virulence, including botulism toxin A3. Of 521 hypothetical proteins, many are involved in amino acid metabolism, and we predicted 13 new virulence proteins. A global regulatory network model revealed 12 transcriptional regulators homologous to Bacillus subtilis, controlling virulence factors. A recombinant subunit and multi-epitope vaccine were developed, targeting proteins such as peptidoglycan hydrolase and SCP-like extracellular protein, showing stable interactions with immune receptors. These vaccines, with minimal allergenicity, are promising candidates against A3 strain virulence. Network modeling revealed host-microbe-drug interactions, identifying linoleic acid as a key metabolite. Chloroquine was found effective for treating foodborne infections, supporting antibiotic repurposing without harming beneficial gut microbes.