| Summary: | Infection with <i>Clostridioides difficile</i> (CDI), a common healthcare-associated infection, includes symptoms ranging from mild diarrhea to severe cases of pseudomembranous colitis. Toxin A (TcdA) and toxin B (TcdB) cause cytotoxicity and cellular detachment from intestinal epithelium and are responsible for CDI symptomatology. Approximately 20% of <i>C. difficile</i> strains produce a binary toxin (CDT) encoded by the <i>tcdA</i> and <i>tcdB</i> genes, which is thought to enhance TcdA and TcdB toxicity; however, the role of CDT in CDI remains controversial. Here, we focused on describing the main features of CDT and its impact on the host, clinical relevance, epidemiology, and potential therapeutic approaches.
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