Genome Of Potential Bioterror Agent Seqenced; Highlights Similarities Between Animal, Plant Pathogens

TIGR's analysis of that sequence and related genomes found "fundamental similarities" between the genome of Brucella – a pathogen that infects only animals -- and other microbes that cause diseases in plants or live symbiotically with plants.

"This study suggests that the genomic differences between animal and plant pathogens are not nearly as wide as scientists used to believe," said Ian Paulsen, Ph.D., the faculty member at TIGR who led the sequencing project. "It seems that plant and animal pathogens may employ similar mechanisms to cause disease."

The complete genome sequence of B. suis, published this week in the online edition of the Proceedings of the National Academy of Sciences (PNAS), provides valuable insights into the lifestyle, pathogenesis and evolution of the potential bioterror agent.

As part of the research project, TIGR scientists compared B. suis with the genome of Brucella melitensis, a related species that causes similar "brucellosis" disease in goats rather than swine. (Both species also affect humans.) They found that the two genomes have a "high degree of similarity," and that most of the differences appear to involve surface-exposed genes such as outer membrane proteins and membrane transporters. "These more variable genes may significantly contribute to the differences in pathogenicity or host preference between these two organisms," the researchers write.

Paulsen said such comparisons are important because they shed light on the molecular mechanisms that enable closely-related species to target different host animals. The TIGR analysis revealed that the major genomic differences result from "phage insertions" – that is, genes that originated in phages (viruses that infect bacteria), which then inserted them into the Brucella genomes.

"These are closely-related pathogens that cause essentially the same disease, but in different host animals --swine and goats," said Paulsen of the two Brucella species. "At present, we know very little about why a pathogen chooses one host and not another – fundamental issues if we want to understand the evolution of human pathogens."

At the moment, there are no acceptable vaccines to immunize humans against B. suis, which is seldom fatal to people but can cause a severe long-term debilitating illness. Persons contract the disease through contact with the tissues of infected animals, by eating contaminated foods, or by inhaling the pathogen.

B. suis is considered to be a potential bioweapon/bioterror agent, selected for "weaponization" in the 1950s because it is highly infectious, debilitates people without usually killing them, and is not transmitted from human to human. Its flu-like disease symptoms make early diagnosis difficult and treating the disease requires prolonged antibiotic therapy.

During the 1950s and 1960s, the U.S. Army had developed artillery shells and bombs armed with B. suis. But that stockpile was destroyed after the U.S. government halted its biowarfare program in 1969. Other countries also developed Brucella weapons during the Cold War.

Claire M. Fraser, Ph.D., president and director of TIGR, said: "The B. suis sequencing project provides important new information about this infectious agent. Genomics has helped us understand more about this pathogen and its closest relatives and defines a new starting point for development of novel methods to diagnose and treat the disease it causes."

The B. suis project was supported by the Defense Advanced Research Projects Agency (DARPA) and by the National Institute of Allergy and Infectious Diseases (NIAID). The paper's authors include researchers at TIGR; the Center for Molecular Medicine and Infectious Diseases at Virginia Tech in Blacksburg, Virginia; the USDA Agriculture Research Service's National Animal Disease Center in Ames, Iowa; and the Walter Reed Army Institute of Research's Division of Communicable Diseases and Immunology in Silver Spring, Maryland

The Institute for Genomic Research (TIGR) is a not-for-profit research institute based in Rockville, Maryland. TIGR, which sequenced the first complete genome of a free-living organism in 1995, has been at the forefront of the genomic revolution since the institute was founded in 1992. TIGR conducts research involving the structural, functional, and comparative analysis of genomes and gene products in viruses, bacteria, archaea, and eukaryotes – higher animals and plants.

The laboratories of the Center for Molecular Medicine and Infectious Diseases (CMMID) are part of the Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech in Blacksburg, Va. The center provides expertise, method development and support services in the area of molecular biology, with a special emphasis on the use of recombinant DNA technology, microarray construction and analysis, BSL-3 laboratory and animal facilities, immunology, and mammalian cell culture in the investigation of infectious diseases and the development and testing of vaccines and diagnostic tests.

The National Animal Disease Center, an arm of the Agricultural Research Service, is the major U. S. Department of Agriculture center for research on livestock and poultry diseases that occur in the United States. The mission of NADC, based in Ames, Iowa, is to conduct basic and applied research on selected diseases of economic importance to the U.S. livestock and poultry industries.

The Walter Reed Army Institute of Research, which is the largest, most diverse, and oldest laboratory in the U.S. Army Medical Research and Materiel Command, conducts research on a range of militarily relevant issues, including naturally occurring infectious diseases, combat casualty care, operational health hazards, and medical defense against biological and chemical weapons. WRAIR is the Department of Defense's lead institute for infectious disease research and a crucial source of research support for medical product development.