Foodborne Bacterial Pathogens
- Our primary objective is to study the biology of C. botulinum in order to better understand the mechanisms underlying regulation of neurotoxin formation, lag time, and genetic and phenotypic variation, and the consequences of these for risk assessment.
Botulism is a deadly disease, and Clostridium botulinum is of great strategic importance to the food industry and regulators (foodborne botulism), the medical and health community (infant/intestinal botulism and wound botulism), the pharmaceutical industry, and has particular relevance to defending against bioterrorism. We have internationally-recognised expertise in anaerobic microbiology, especially with C. botulinum, a difficult and dangerous pathogen to work with. Recent developments in clostridial molecular biology now make this an exciting time to work on clostridia. We will take advantage of, and build up our molecular genetic toolkit for C. botulinum. We have contributed to the genome sequencing of proteolytic C. botulinum strain Hall A, and the sequence of non-proteolytic C. botulinum strain Eklund 17B is in progress. Our research focuses on these two strains.
We have developed in-house DNA microarrays, applied transcriptomic technology to C. botulinum, and used a novel plasmid-based system to up-regulate specific genes, and are adopting the ClosTron system to inactivate specific genes. With this toolkit, we now have an outstanding opportunity to determine the molecular basis of the physiological responses of C. botulinum when subjected to food- and gut-relevant stresses. This includes determining the molecular mechanisms underlying the physiological strategies used by C. botulinum to begin growth, and identifying the transcriptional programming responsible for germination and neurotoxin production by this bacterium. We are characterising genotypic/phenotypic variation between strains of C. botulinum, and how this impacts on the fitness of C. botulinum as a pathogen.