Outlining mechanisms behind super infectious bacteria
C. difficile, also referred to as a 'superbug', is causing severe health problems across Europe due to the emergence of antibiotic-resistant strains. Identification of the genes involved in infection and disease progression will permit the development of more effective diagnostic tests and treatments for C. difficile. The project HYPERDIFF (The physiological basis of hypervirulence in Clostridium difficile: a prerequisite for effective infection control) investigated the physiological factors causing hypervirulence in C. difficile. The aim was to formulate more effective countermeasures for infection control and disease management. Project partners’ approach was to inactivate genes that encode products involved in pathogenesis. This was achieved through the revolutionary ClosTron mutant generation technology developed by one of the university partners to study virulence-related genes. Pathogenic bacteria produce several toxins, with toxin A (enterotoxin) and B (cytotoxin) being the most well characterised. Scientists showed that toxin A was sufficient to induce disease, illustrating the importance of targeting both toxins in therapeutic regimens. C. difficile hypervirulence was also shown to be mediated by adherence proteins, possibly offering some ecological advantage to the bacterium to colonise the gastrointestinal tract. Compelling evidence was generated against the current dogma that hypervirulent strains are more prolific in terms of spore formation. HYPERDIFF researchers showed that the majority of C. difficile mobile genetic elements were transferrable, allowing for recipient strains to cause disease. Analysis of a database of human and animal C. difficile isolates provided novel insight. Data revealed that the isolates obtained from human infections in the community closely resembled those obtained from pet and farm animals rather than those encountered in hospitals. This indicated that animals acted as a reservoir for human infection, at least in the community. Long-term, identification of the most important factors for virulence and tissue colonisation by HYPERDIFF will enable the formulation of more efficient therapeutic drugs and protective vaccines to prevent and treat disease outbreaks.
Keywords
Hypervirulent, Clostridium difficile, HYPERDIFF, ClosTron, toxin A