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 on September 9th 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 bacteria in humans, Y. pestis was responsible for the bubonic plague, or “Black Death,” that killed millions of people in Asia and Europe in the Middle Ages.
Most Y. pestis strains are treatable with antibiotics. If left untreated, however, bubonic plague is lethal in 70 percent of the cases, usually with a week; while pulmonary plague, acquired by breathing the bacteria, is almost always fatal within two to three days.
The last urban plague epidemic in the United States occurred in Los Angeles in 1924-25. An average of 10 to 15 cases in the United States, and between 1,000 and 3,000 cases worldwide, are reported every year. The disease has long been considered a prime candidate for bioterrorism because of its extreme virulence and its potential to be spread through the air as well as by infected fleas.