Advances in Understanding the Pathogenesis of Clostridioides difficile Infection.

Infect Dis Clin North Am

Department of Microbiology, Institute for Immunology and Immune Health, University of Pennsylvania Perelman School of Medicine, 303B Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.

Published: September 2025


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Article Abstract

Clostridioides difficile infection (CDI) remains a significant cause of infectious colitis in the United States. Susceptibility to CDI is associated with perturbation of the gut microbiota, the indigenous microbes in the gastrointestinal tract. Upon colonization, the production of toxins and the ability to produce spores for environmental dissemination contribute to C difficile pathogenicity. Regulation of the virulence genes governing these processes are interconnected with C difficile metabolism and interactions with other gut microbes. This review summarizes these pathogenic aspects, with a focus on recent data illustrating additional mechanisms that modulate colonization and toxin-mediated disease during CDI development.

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http://dx.doi.org/10.1016/j.idc.2025.07.001DOI Listing

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