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Missing genes may help explain why plague bacteria are so deadly

LIVERMORE, Calif. What makes the germ that causes plague so fearsomely lethal, while a close relative only produces digestive disorders and is rarely fatal?

The answer may be in its genes or rather, its lack of them.

By comparing the genome of the plague bacillus, Yersinia pestis, with the almost-identical DNA sequence of Yersinia pseudotuberculosis, an international team led by researchers at Lawrence Livermore National Laboratory (LLNL) has found that several hundred genes that apparently were inactivated as the plague bacterium evolved may be largely responsible for its virulence.

In a report published today (Sept. 9) in the online edition of the Proceedings of the National Academy of Sciences, the researchers said the "massive gene loss" and DNA rearrangements that occurred as Y. pestis evolved "provide a sobering example of how a highly virulent epidemic (pathogen) can suddenly emerge from a less virulent, closely related progenitor."

"This work is seminal because it has enabled us for the first time to follow the precise molecular events that led to the emergence of this highly virulent bacterium," said LLNL biologist Emilio Garcia, who headed the research team.

Knowledge of the genetic factors that contribute to the plague bacteria's virulence could aid researchers in developing better ways to detect, prevent, and treat the deadly disease.

The LLNL research, conducted in conjunction with the Yersinia Research Unit of the Institut Pasteur in Paris and several other organizations, suggests that natural selection may have led to the inactivation of genes in Y. pestis that tended to suppress its lethality, possibly giving it an evolutionary leg up on its more benign cousins.

Evolutionary pressures may have also made the bacterium better adapted to colonize the flea, its preferred vector (means of transmission), and thus facilitate the flea-borne spread of the disease.

Perhaps the most infectious of all bacter
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Contact: Charlie Osolin
osolin1@llnl.gov
925-422-8367
DOE/Lawrence Livermore National Laboratory
9-Sep-2004


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