Scientists map tuberculosis genome

Thursday June 11 2:34 PM EDT

NEW YORK, Jun 10 (Reuters) -- The genetic blueprint, or genome, of the tuberculosis bacterium has now been fully documented by a team of European researchers.

"The sequence marks a new phase in the battle against one of mankind's most successful predators," said Dr. Douglas Young of the Imperial College School of Medicine in London, England.

His commentary, and a report by the team responsible for sequencing the genome, are published in the current issue of the journal Nature. Mycobacterium tuberculosis, first isolated in 1905, is thought to have originated as a soil-borne pathogen and adapted to residence within human lung tissue over 10,000 years ago. The bacillus is unusual among bacteria in that it has a relatively slow reproductive cycle (24 hours), long periods of dormancy, and little genetic variance between individual isolates.

Still, despite advances in hygiene, living conditions and antibiotics, tuberculosis continues to spread throughout the developed and developing world. This spread has been encouraged in recent years by what Young calls "a deadly partnership" between Mycobacterium tuberculosis and HIV, which lowers human immune resistance to tuberculosis infection.

However, the sequencing of all 4,411,529 base pairs that make up the 'rungs' on the tuberculosis bacterium's DNA gene 'ladder' has now been completed by Dr. Stewart Cole and others at the Wellcome Trust Genome Campus in Hinxton, UK. They say these base pairs combine to form over 4,000 individual genes.

Reporting in Science, the researchers say the genome is already yielding information that could prove invaluable to future research.

First of all, they note that a large proportion of the genome focuses on enzymes necessary for the breakdown of fatty acids found in animal cells. The promise of a better understanding of the genetic underpinnings of these processes "provides a cornucopia of potential drug targets," according to Young.

Secondly, Cole and his team have discovered that about 10% of the genome is devoted to the production and function of two types of proteins, called PE and PPE. These proteins are also present in other infectious microorganisms, which use them to disarm or avoid human immune defenses.

Young explains that "by altering the patterns by which these proteins are expressed, pathogens (including, perhaps, Mycobacterium tuberculosis) present the immune system with a moving target, thereby increasing their chances of survival." Experts believe study focused on these protein-driven mechanisms may present a new and exciting avenue of tuberculosis vaccine research. SOURCE: Nature 1998;393:537-544, 545-546.

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