title: Silencing urease: a key evolutionary step that facilitated the adaptation of Yersinia pestis to the flea-borne transmission route.
abstract: The arthropod-borne transmission route of Yersinia pestis, the bacterial agent of plague, is a recent evolutionary adaptation. Yersinia pseudotuberculosis, the closely related food-and water-borne enteric species from which Y. pestis diverged less than 6,400 y ago, exhibits significant oral toxicity to the flea vectors of plague, whereas Y. pestis does not. In this study, we identify the Yersinia urease enzyme as the responsible oral toxin. All Y. pestis strains, including those phylogenetically closest to the Y. pseudotuberculosis progenitor, contain a mutated ureD allele that eliminated urease activity. Restoration of a functional ureD was sufficient to make Y. pestis orally toxic to fleas. Conversely, deletion of the urease operon in Y. pseudotuberculosis rendered it nontoxic. Enzymatic activity was required for toxicity. Because urease-related mortality eliminates 30-40% of infective flea vectors, ureD mutation early in the evolution of Y. pestis was likely subject to strong positive selection because it significantly increased transmission potential.
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840 iman.chouikha@nih.gov.
authors.forename: Iman
authors.initials: I
authors.lastname: Chouikha
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D020868:Gene Silencing; D006801:Humans; D007303:Insect Vectors / Q000382:microbiology*; D009154:Mutation; D010930:Plague / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000635:transmission; D014510:Urease / Q000235:genetics / Q000378:metabolism; D058260:Xenopsylla / Q000382:microbiology*; D015010:Yersinia pestis / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D015011:Yersinia pseudotuberculosis / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; C086767:UreD protein, Bacteria; D014510:Urease
keywords: Yersinia urease; arthropod-borne transmission; evolution; plague; pseudogene