TheYersinia pestis caf1M1A1Fimbrial Capsule Operon Promotes Transmission by Flea Bite in a Mouse Model of Bubonic Plague

Abstract

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.

Host Specificity of Bacterial Pathogens

“…For instance, the ymt gene located on the pFra plasmid encodes phospholipase D, which enhances the ability of Y. pestis to colonize the flea midgut (Hinnebusch et al 2002). The pFra plasmid also carries the caf1M1A1 operon, which encodes a protein capsule that is required for infection of mice by the flea-borne route (Sebbane et al 2009). The pla gene carried on the pPst plasmid encodes a plasminogen activator that is specifically required for inducing the bubonic form of plague in the mouse after a flea bite (Sebbane et al 2006).…”

Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

“…Sebbane and colleagues 50 reported that F1 pili contribute to the transmission of plague via flea bite; however, F1 is not essential for bubonic or pneumonic plague in mice. 20 Herein, we report that F1 variants, engineered or naturally acquired, are less likely to cause bubonic plague after s.c. injection into guinea pigs.…”

Characterizing the virulence factor YapE in Yersinia pestis.

“…Caf1 capsule is strongly influenced by temperature, where essentially no capsule is identified in the flea vector or at temperatures <35°C [54]. The caf1 gene is the most highly expressed genes during infection of the mammal, indicating that it is a virulence factor [54].…”

“…The Caf1 capsule is made up of the Fraction 1 (F1) antigen, a fimbrial protein that accrues on the bacterial surface to form a capsule unique to Y. pestis [54].…”

“…The caf1 gene is the most highly expressed genes during infection of the mammal, indicating that it is a virulence factor [54]. Studies have shown that the capsule works in tandem with the T3SS to make Y. pestis resistant to uptake by macrophages and PMNs [55][56][57][58].…”