Pathogenicity and virulence of Clostridioides difficile

Clostridioides difficile is the most common cause of nosocomial antibiotic-associated diarrhoea, and is responsible for a spectrum of diseases characterised by high levels of recurrence, morbidity and mortality. Treatment is complex, since antibiotics constitute both the main treatment and the major risk factor for infection. Worryingly, resistance to multiple antibiotics is becoming increasingly widespread, leading to classification of this pathogen as an urgent threat to global health. As a consummate opportunist, C. difficile is well-equipped for promoting disease, owing to its arsenal of virulence factors: transmission of this anaerobe is highly efficient due to formation of robust endospores, and an array of adhesins promote gut colonisation. C. difficile produces multiple toxins acting upon gut epithelia, resulting in manifestations typical of diarrhoeal disease, and severe inflammation in a subset of patients. This review focuses on such virulence factors, as well as the importance of antimicrobial resistance and genome plasticity in enabling pathogenesis and persistence of this important pathogen.