Clostridium difficile infection (CDI) presents a major clinical and economic challenge to public health systems, reaching an epidemic state in some regions of the world. In Australia, increasing rates of community-acquired CDI (now accounting for 30% of all cases) suggest exposure to C. difficile reservoirs outside the hospital, including animals, food or the environment. Indeed, Australian livestock are a significant reservoir for evolutionary lineages of C. difficile causing CDI in humans. The amplification of C. difficile in production animal systems and subsequent contamination of meat, vegetables grown in soil containing animal faeces, and agricultural by-products such as compost and manure, is driving the insidious rise of CDI in the community.

One Health is a philosophical approach to improving and safeguarding the health of humans, animals and the environment and, importantly, recognises that these three areas are inter-related. In this regard, CDI is the quintessential One Health issue. The application of high-resolution microbial genomics in a One Health framework has yielded critical insights into the evolution and transmission of C. difficile in humans and animals, and their shared environment. This talk will provide an overview of our recent genomic investigations that provide substantive evidence of transmission between livestock and humans of two lineages of C. difficile of One Health importance (ribotype 014 and sequence type 11). These findings provide compelling evidence of a zoonosis and challenge the existing paradigm that CDI is exclusively a healthcare-associated infection.