HYPERDIFF · The Physiological Basis of Hypervirulence in Clostridium difficile: a Prerequisite for Effective Infection Control

Clostridium diffficile is currently wreaking havoc within European health systems due to the emergence of hyper virulent strains, responsible for more severe disease, higher relapse rates, increased mortality and greater resistance to antibiotics. Its impact in healthcare settings is considerable, in terms of morbidity, mortality and financial cost However, the physiological basis of pathogenesis is poorly understood due to an absence of mutational tools for functional genomic studies. This bottleneck has been solved by partner 1 who has developed the ‘ClosTron’, a highly efficient gene knock-out tool. This will be used to systematically inactivate those chromosomal genes which encode products hypothesised to be involved in pathogenesis, and an assessment of the consequences made in models of infection. To ascertain the prevalence of the identified hyper virulence traits in the human and animal population, epidemiological studies will be undertaken. Special attention will be paid to the wider human population to gauge the prevalence of community acquired C. difficile. The identity of the determinants responsible for hyper virulence would allow the derivation of diagnostic tests directed specifically at those factors directly responsible for their spread within the healthcare setting. They will also allow the formulation of therapeutic countermeasures that could be deployed to both prevent and treat disease outbreaks. The objectives of HYPERDIFF will be met by a consortium of the leading EU researchers on C. difficile. It brings together a multidisciplinary team from a range of sectors and 6 member states. They are composed of 4 Universities, 2 Government Institutes, and a commercial company, with the key skills needed to deliver the objectives of HYPERDIFF. In combination with the unique ClosTron system, these capabilities will propel Europe to the forefront of the field.