Work Could Lead to Better Vaccines and Treatment of Highly Infectious Disease
LIVERMORE, Calif. - Two teams of researchers, one based in the United States and the other in Europe, have decoded the genetic blueprint of the tularemia (rabbit fever) bacterium, a highly infectious human and animal pathogen.
The complete genomes of separate strains of Francisella. tularensis were sequenced by scientists at the U.S. Department of Energy's Lawrence Livermore National Laboratory (LLNL) in California and at Uppsala University in Uppsala, Sweden. Also participating were researchers at Porton Down, United Kingdom; the Swedish Defense Agency, Umea, Sweden; the U.S. Center for Disease Control's Division of Vector-Borne Infectious Diseases, Fort Collins, Colo.; and Walter Reed Army Institute of Research, Silver Spring, Md.
"Comparing the genome sequences of the two strains will help us identify the genes, and their associated proteins, that cause one strain of F. tularensis to be more virulent than another," said biologist Emilio Garcia, one of the project leaders for the Laboratory.
Knowledge of the microbe's genome sequence - the precise order of the nucleotide bases in its DNA - can improve scientific understanding of its fundamental physiology and metabolism. The knowledge could help researchers develop more effective vaccines and better methods for detecting, diagnosing and treating tularemia.
Tularemia is a rare but serious disease normally spread by insect bites and human contact with rabbits, prairie dogs, and other small and medium-sized animals. While seldom fatal, and treatable with antibiotics, the disease causes severe, long-lasting pneumonia-like symptoms and a variety of glandular and intestinal disorders. As few as 10 organisms entering the body can cause fever, making tularemia one of the most infectious of all human diseases.
First discovered in 1911, tularemia is an "intracellular" pathogen that invades the body's cells, shuts down their normal immune response, and then multiplies within the body. The bacteria can enter the body through open wounds, inhalation, ingestion, or bites from ticks and deerflies. Signs of pneumonia and fever typically arise 24 to 48 hours after the disease is contracted.
While the virulent SchuS4 strain sequenced by Uppsala University is found primarily in North America, the microbe sequenced by LLNL, known as F. tularensis LVS (Live Vaccine Strain), is more widespread yet less virulent and is found in North America, Europe, and Northeast and Central Asia.
An annual average of about 125 human cases of the disease were reported in the United States in the 1990s. In addition to being found naturally in the environment, F. tularensis is considered a potential biothreat agent. Prompt treatment with antibiotics can head off the worst symptoms of tularemia, which is currently fatal in about 2 percent of reported cases.
The F. tularensis LVS sequence, consisting of about 1.9 million base pairs, is being published on LLNL's website ( http://bbrp.llnl.gov/bbrp/html/microbe.html ). The F. tularensis SchuS4 sequence is available at
http://artedi.ebc.uu.se/Projects/Francisella . Once they are fully annotated, both sequences will also be submitted to Genbank, the DNA sequence database maintained by the U.S. National Institutes of Health, so they can be accessed and studied by scientists around the world.
The Livermore project was funded by DOE and other U.S. federal agencies, as well as by Laboratory Directed Research and Development funds. The European-American consortium was funded by the U.S. Army Medical Research and Materiel Command, the UK Ministry of Defense, the Swedish Ministry of Defense, and the U.S. Defense Advanced Research Projects Agency.
Founded in 1952, Lawrence Livermore National Laboratory is a national security laboratory, with a mission to ensure national security and apply science and technology to the important issues of our time. Lawrence Livermore National Laboratory is managed by the University of California for the U.S. Department of Energy's National Nuclear Security Administration.