Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague

Abstract

Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread.vector-borne disease

Host Specificity of Bacterial Pathogens

“…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). Thus, acquisition of two Y. pestisspecific plasmids by lateral gene transfer facilitated the rapid evolutionary transition of Y. pestis to flea-borne transmission.…”

Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague

“…The 9.5-kb pPla plasmid encodes the Y. pestis plasminogen activator (Pla) (McDonough and Falkow 1989;Sodeinde and Goguen 1988). Although Pla is not required to produce a transmissible infection in the flea or to cause the low-incidence primary septicemic form of plague following flea-bite transmission, it is required for systemic dissemination and the development of bubonic plague following intradermal injection of Y. pestis by fleabite or by needle (Brubaker et al 1965;Hinnebusch et al 1998;Sebbane et al 2006;Sodeinde et al 1992). …”

Capsular Antigen Fraction 1 and Pla Modulate the Susceptibility of Yersinia pestis to Pulmonary Antimicrobial Peptides Such as Cathelicidin

“…Pla is also a mediator of bacterial binding to extracellular matrix proteins such as laminin (35). Pla is essential for bubonic plague (but not for septicemic plague) after flea-mediated transmission (53,57,68). Pla is also essential for the development of (but not dissemination of) primary pneumonic plague (36).…”