| Summary: | <i>Clostridioides difficile</i> was first identified in 1935 and subsequently emerged over the next several decades as the predominant bacterial cause of healthcare-associated gastrointestinal infections, placing a significant burden on healthcare systems worldwide. A major driver of the rapid rise in the incidence of <i>C. difficile</i> infection (CDI) was the emergence and spread of a hypervirulent strain, which became known as PCR ribotype 027 (RT027). The <i>C. difficile</i> RT027 strain produced not just the typical toxin A and toxin B virulence factors but also expressed a third toxin called binary toxin that enhanced pathogenicity. Interestingly, the <i>C. difficile</i> RT027 strain apparently emerged at least twice in geographically distinct areas. The two lineages can be differentiated by their resistance or susceptibility to fluoroquinolones. Other ribotypes of <i>C. difficile</i> that also express binary toxin have emerged recently, some of which are highly related genetically to RT027. The aim of this study is to integrate genomic data and published literature to clarify the emergence, divergence, and apparent decline of <i>C. difficile</i> RT027.
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