Pathogenicity and virulence of Clostridioides difficile

ABSTRACT

Clostridioides difficile is the most common cause of nosocomial antibiotic-associated diarrhea, and is responsible for a spectrum of diseases characterized 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 the 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 the formation of robust endospores, and an array of adhesins promote gut colonization. C. difficile produces multiple toxins acting upon gut epithelia, resulting in manifestations typical of diarrheal 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.

KEYWORDS:

• c. difficile
• virulence factors
• antimicrobial resistance
• toxins
• spores
• CDI

Acknowledgments

Work in the RPF laboratory is currently supported by grants from the BBSRC (BB/P02002X/1), MRC (MR/S009272/1), and Wellcome Trust (204877/Z/16/Z). JEB is supported by a studentship from the MRC Discovery Medicine North (DiMeN) Doctoral Training Partnership (MR/R015902/1).

Disclosure statement

RPF has an active collaboration with Summit Therapeutics and they are CASE partner for JEB’s PhD studentship.

Additional information

Funding

The work was supported by the BBSRC [BB/P02002X/1]; Medical Research Council (MRC) [MR/R015902/1]; Medical Research Council (MRC) [MR/S009272/1]; Wellcome Trust [204877/Z/16/Z].