e-journal
The Yersinia pestis caf1M1A1 Fimbrial Capsule Operon Promotes Transmission by Flea Bite in a Mouse Model of Bubonic Plague
Plague is a zoonosis transmitted by fleas and caused by the gram-negative bacterium Yersinia pestis. During
infection, the plasmidic caf1M1A1 operon that encodes the Y. pestis 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 Y. pestis strains are rarely
isolated. We found that a caf-negative Y. pestis mutant was not impaired in either flea colonization or virulence
in mice after intradermal inoculation of cultured bacteria. In contrast, absence of the caf operon decreased
bubonic plague incidence after a flea bite. Successful development of plague in mice infected by flea bite with
the caf-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 caf locus via horizontal transfer by an ancestral Y. pestis strain increased transmissibility and the
potential for epidemic spread. In addition, our data support a model in which atypical caf-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 Y. pestis strains in plague foci may be necessary. The results also
highlight the importance of studying Y. pestis pathogenesis in the natural context of arthropod-borne
transmission.
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