Adaptation of host transmission cycle during Clostridium difficile speciation

Nitin Kumar, Hilary P. Browne, Elisa Viciani, Samuel C. Forster, Simon Clare, Katherine Harcourt, Mark D. Stares, Gordon Dougan, Derek J. Fairley, Paul Roberts, Munir Pirmohamed, Martha R.J. Clokie, Mie Birgitte Frid Jensen, Katherine R. Hargreaves, Margaret Ip, Lothar H. Wieler, Christian Seyboldt, Torbjörn Norén, Thomas V. Riley, Ed J. KuijperBrendan W. Wren, Trevor D. Lawley

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)


    Bacterial speciation is a fundamental evolutionary process characterized by diverging genotypic and phenotypic properties. However, the selective forces that affect genetic adaptations and how they relate to the biological changes that underpin the formation of a new bacterial species remain poorly understood. Here, we show that the spore-forming, healthcare-associated enteropathogen Clostridium difficile is actively undergoing speciation. Through large-scale genomic analysis of 906 strains, we demonstrate that the ongoing speciation process is linked to positive selection on core genes in the newly forming species that are involved in sporulation and the metabolism of simple dietary sugars. Functional validation shows that the new C. difficile produces spores that are more resistant and have increased sporulation and host colonization capacity when glucose or fructose is available for metabolism. Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple dietary sugars and producing high levels of resistant spores, that is adapted for healthcare-mediated transmission.

    Original languageEnglish
    Pages (from-to)1315-1320
    Number of pages6
    JournalNature Genetics
    Issue number9
    Publication statusPublished - Sep 2019


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