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.

To get at the genetic basis for the deadly nature of Y. pestis, the Livermore-led researchers first sequenced the complete genome of Y. pseudotuberculosis, an animal and human pathogen that can cause fever and appendicitis-like pain if ingested in water or food. They then compared the Y. pseudotuberculosis genome with the DNA sequences of two Y. pestis strains previously sequenced by the Sanger Institute in Cambridge, England.

While the comparison revealed a number of genes in the plague bacterium that are not present in its relative, Garcia said the more important finding was the extent and apparent cause of gene inactivation in Y. pestis.

"As many as 13 percent of Y. pseudotuberculosis genes no longer function in Y. pestis," he said. "We found that the number of insertion sequence (IS) elements (DNA sequences capable of interfering with gene expression) has dramatically expanded in Y. pestis, delineating the probable role of IS expansion in the elimination and modification of preexisting gene expression pathways."

Sequencing of the Y. pseudotuberculosis genome was part of a "Bio-foundation Initiative" funded by the U.S. Dep
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Contact: Charlie Osolin
osolin1@llnl.gov
925-422-8367
DOE/Lawrence Livermore National Laboratory
9-Sep-2004