Bioterror Bacterium Genome Deciphered

'Stealth' properties of highly infectious organism surprise scientists

WEDNESDAY, Dec. 26 , 2001 (HealthDayNews) -- Scientists have deciphered the genetic blueprint of a highly infectious organism considered to be a potential bioterrorism weapon.

A report by an international team of researchers describes the genome sequence for Brucella melitensis, a bacterium that causes brucellosis, also known as Malta fever or undulant fever.

The findings, which appear in today's issue of the Proceedings of the National Academy of Sciences journal, could lead to new therapies or vaccines against the disease, which the lead investigator calls "much more infectious than anthrax."

"With anthrax, you need 10,000 to 20,000 spores to get inhalation anthrax. With Brucella melitensis, you need just one cell," says Vito DelVecchio, director of research at the University of Scranton's Institute of Molecular Biology and Medicine, in Pennsylvania.

Primarily a disease in animals, cattle and pigs in particular, brucellosis can be transmitted to other animals or to humans through direct skin contact or inhalation of infective droplets or dust. In humans, the bacterium causes symptoms ranging from fever, severe sweating and fatigue, to arthritis and dementia.

"The dementia really clouds up or impairs the reasoning process, which, if you think in terms of biological warfare, could be horrible," says DelVecchio, whose laboratory has studied organisms, including anthrax, that have potential as biological weapons.

While the Centers for Disease Control and Prevention usually monitors about 100 cases a year in the United States, DelVecchio says the disease "is a terrible problem in the Middle East and in Europe. Brucellosis is endemic there."

To decipher the genetic blueprint, the researchers determined that the bacterium has more than 3.2 million base pairs split between two chromosomes. A single chromosome is common to most bacteria.

"At one point in evolution, it was probably one big chromosome, and it probably split off into two," DelVecchio says.

The genome also surprised the researchers. "The organism does not have what you usually see as a very strong, big pathogenecity factor," says DelVecchio, meaning that no one part of the genome is obviously responsible for making the host sick. Other bacteria, such as Escherichia coli, produce a specific toxin that makes people ill.

"This organism is very stealth-like," DelVecchio says. It appears to get inside the host's cells, where it sets up shop and divides along with the host's cells. Although it's not exactly clear how Brucella melitensis makes people sick, he says it appears that symptoms appear when the host begins to react to the presence of the bacteria.

"If you have brucellosis, you have to be on two antibiotics for a period of at least six months to a year, because the relapse rate is very, very high. It's intracellular, which means it's hard for the antibiotics to get to the organism," he says.

A human vaccine against brucellosis has not materialized because modifying the organism to make it harmless while still conferring immunity is difficult, he says.

"Now we not only know the genome, but it's one of the most highly annotated genomes," he says. "We've identified what the genes are and what proteins they give rise to."

By combining the finding with studies of mutant Brucella melitensis strains, DelVecchio says he hopes to point the way to new vaccines. His researchers are studying ways to rapidly detect infection. They're also studying exactly what the organism does inside a host and what the host does to respond to the organism. "This will give us a great deal of information in terms of treatment," he says.

Fred Enright, a brucella researcher in the department of veterinary sciences at Louisiana State University, in Baton Rouge, says the genome will answer questions about how the organism causes disease and will point to potential vaccine and diagnostic approaches.

"Once you know what the genetic factors are, then you have a rational way to alter the genetics of that organism to allow you to produce organisms which aren't pathogenic and can therefore be used as possible vaccines," Enright says.

What to Do: Find out more about brucellosis from the Centers for Disease Control and Prevention, the Workers Health Centre or the U.S. Department of Agriculture.

SOURCES: Interviews with Vito G. DelVecchio, Ph.D., director of research, Institute of Molecular Biology and Medicine, University of Scranton, Pa.; Fred M. Enright, D.V.M., Ph.D., professor, department of veterinary sciences, Louisiana State University, Baton Rouge, La.; Dec. 26, 2001, Proceedings of the National Academy of Sciences
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