Silencing urease: A key evolutionary step that facilitated the adaptation of Yersinia pestis to the flea-borne transmission route

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 52; pp. 18709 - 18714
• Main Authors: Chouikha, Iman, Hinnebusch, B. Joseph
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 30.12.2014; National Acad Sciences
• Series: From the Cover
• Subjects: acute toxicity; Animals; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological Sciences; dietary exposure; Disease transmission; Ecological adaptation; enteropathogens; Enzymatic activity; Enzymes; essential genes; Evolution; Evolution, Molecular; Fleas; Gene Silencing; Humans; Infections; Insect Vectors - microbiology; Mortality; Mutation; Plague; Plague - enzymology; Plague - genetics; Plague - pathology; Plague - transmission; probability; Siphonaptera; Toxicity; Toxins; urease; Urease - genetics; Urease - metabolism; Xenopsylla - microbiology; Yersinia; Yersinia pestis; Yersinia pestis - enzymology; Yersinia pestis - genetics; Yersinia pestis - pathogenicity; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis - enzymology; Yersinia pseudotuberculosis - genetics; Yersinia pseudotuberculosis - pathogenicity; Yersinia urease; pseudogene; evolution; plague; arthropod-borne transmission
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1413209111

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. Significance The plague bacillus Yersinia pestis is transmitted by fleas but evolved very recently from Yersinia pseudotuberculosis , a closely related food- and water-borne enteric pathogen. Identifying the specific genetic changes underlying the switch to arthropod-borne transmission is essential to understanding the evolution of Y. pestis and the emergence of plague. We have identified an important early step in this process. The urease enzyme, beneficial for an enteric bacterium, causes acute oral toxicity and significant mortality to fleas. Y. pestis is not toxic to fleas because of a loss-of-function mutation in one of the genes essential for urease activity. Epidemiologic modeling suggests that this mutation was positively selected during evolution because it resulted in a significantly higher probability of Y. pestis transmission.