A single gene change in a relatively benign recent ancestor of the bacterium that causes bubonic plague played a key role in the evolution of the deadly disease, researchers report in the April 26 issue of the journal Science. By acquiring this gene, the bacterium gradually changed from a germ that causes a mild human stomach illness acquired via contaminated food or water to the flea-borne agent of the "Black Death," which in the 14th century killed one-fourth of Europe's population.
The new research adds an important piece to understanding the forces behind the emergence of plague, which occurred within the past 1,500 to 20,000 years. "Our research illustrates how a single genetic change can profoundly affect the evolution of disease. In this case, that genetic change set the stage for a completely new route of disease transmission," notes B. Joseph Hinnebusch, Ph.D., lead author of the study and plague expert in Rocky Mountain Laboratories, a Montana outpost of the National Institute of Allergy and Infectious Diseases (NIAID). The gene allowed the bacteria to be transmitted through the bite of an insect - in this case, the flea - an adaptation that distinguishes Yersinia pestis, the plague germ, from all closely related, more benign gut bacteria. In turn, as Y. pestis adapted to rely on its new blood-feeding host for transmission, the emergence of more deadly bacterial strains would have been favored, the researchers conclude.
The evolution of the plague bacterium is just one example of how microbes persistently challenge researchers by unexpectedly repackaging themselves, in any of multiple ways, to emerge as novel or more virulent agents of human disease.
In the new report, Dr. Hinnebusch and his colleagues from Sweden, Michigan, and NIAID describe how they explored the source of this gene and later identified the critical role it plays.
The gene codes for an enzyme known as PLD. Previous work indicated that Y. pestis picked up this gene from either an unrelated bacterium or a simple nucleated organism.
Next the researchers infected fleas with variants of Y. pestis that either contained or lacked the PLD gene and then observed the outcome. They discovered that the enzyme is required for survival of the plague bacterium in the midgut of the rat flea.
Although the enzyme's activity protects Y. pestis from being destroyed, thereby allowing it to colonize the flea gut freely, the researchers do not yet know the molecular mechanism by which this protection occurs. "To find that out is clearly the next step," Dr. Hinnebusch notes.
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Reference: BJ Hinnebusch, AE Rudolph, P Cherepanov, JE Dixon, TG Schwan, and A Forsberg. Role of Yersinia murine toxin in survival of Yersinia pestis in the midgut of the flea vector. Science 296:733-35 (2002).
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The above post is reprinted from materials provided by NIH/National Institute Of Allergy And Infectious Diseases. Note: Content may be edited for style and length.
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