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Two Distinct Transmission Routes Described for the Evolution of Plague

Over millennia of evolution, Yersinia pestis—the bacterial agent of plague—has acquired an enzyme enabling it to attack the lymph system, thus allowing the development of the bubonic form of plague infection.

But this wasn’t the first type of recognized infection caused by Y. pestis, say scientists at NIAID Rocky Mountain Laboratories in Hamilton, Montana. By studying an enzyme known as a plasminogen activator, or Pla, a research group led by B. Joseph Hinnebusch, Ph.D., answered a longstanding question about the origin of the other main type of plague, septicemic plague. Researchers had previously thought that septicemia always followed a lymph system infection rather than direct infection of the bloodstream.

In studies involving laboratory mice, RML scientists used natural fleaborne transmission of Y. pestis to infect the animals. The group used both a common Y. pestis strain found in nature and a mutant strain in which the Pla was removed.

Of 10 mice exposed to the mutant strain by flea bite, three developed septicemic plague while none developed bubonic plague. Of 10 mice exposed to the natural strain by flea bite, eight developed plague, six the bubonic type, and two the septicemic type. The results identified primary septicemic plague as a distinct form of the disease.

The researchers hypothesize that the Pla activity has a role in making human lymph systems vulnerable to Y. pestis infection but is not required if fleas inject bacteria directly into the bloodstream.

Information about this work is available in the April 4, 2006, edition of Proceedings of the National Academy of Sciences.


Sebbane F et al. Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. Proc Natl Acad Sci DOI: 10.1073/pnas.0509544103 (2006).

Dr. Hinnebusch's Lab

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Last Updated November 30, 2006