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During infection, the plasmidic<jats:italic>caf1M1A1<\/jats:italic>operon that encodes the<jats:italic>Y. pestis<\/jats:italic>F1 protein capsule is highly expressed, and anti-F1 antibodies are protective. Surprisingly, the capsule is not required for virulence after injection of cultured bacteria, even though it is an antiphagocytic factor and capsule-deficient<jats:italic>Y. pestis<\/jats:italic>strains are rarely isolated. We found that a<jats:italic>caf<\/jats:italic>-negative<jats:italic>Y. pestis<\/jats:italic>mutant was not impaired in either flea colonization or virulence in mice after intradermal inoculation of cultured bacteria. In contrast, absence of the<jats:italic>caf<\/jats:italic>operon decreased bubonic plague incidence after a flea bite. Successful development of plague in mice infected by flea bite with the<jats:italic>caf<\/jats:italic>-negative mutant required a higher number of infective bites per challenge. In addition, the mutant displayed a highly autoaggregative phenotype in infected liver and spleen. The results suggest that acquisition of the<jats:italic>caf<\/jats:italic>locus via horizontal transfer by an ancestral<jats:italic>Y. pestis<\/jats:italic>strain increased transmissibility and the potential for epidemic spread. In addition, our data support a model in which atypical<jats:italic>caf<\/jats:italic>-negative strains could emerge during climatic conditions that favor a high flea burden. Human infection with such strains would not be diagnosed by the standard clinical tests that detect F1 antibody or antigen, suggesting that more comprehensive surveillance for atypical<jats:italic>Y. pestis<\/jats:italic>strains in plague foci may be necessary. The results also highlight the importance of studying<jats:italic>Y. pestis<\/jats:italic>pathogenesis in the natural context of arthropod-borne transmission.<\/jats:p>","DOI":"10.1128\/iai.00950-08","type":"journal-article","created":{"date-parts":[[2008,12,23]],"date-time":"2008-12-23T01:45:28Z","timestamp":1229996728000},"page":"1222-1229","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["The<i>Yersinia pestis caf1M1A1<\/i>Fimbrial Capsule Operon Promotes Transmission by Flea Bite in a Mouse Model of Bubonic Plague"],"prefix":"10.1128","volume":"77","author":[{"given":"Florent","family":"Sebbane","sequence":"first","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, U801, Institut Pasteur de Lille, Universite\u0301 de Lille 2, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton","family":"Jarrett","sequence":"additional","affiliation":[{"name":"Laboratory of Zoonotic Pathogens"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Gardner","sequence":"additional","affiliation":[{"name":"Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Long","sequence":"additional","affiliation":[{"name":"Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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