Study Identifies Genetic Variation In Tuberculosis Strains
A TIGR comparison of the whole genomes of two strains of the bacterium that causes tuberculosis has found a surprising number of differences, indicating that genetic variation may be more extensive among Mycobacterium tuberculosis isolates than previously thought, and may play an important role in the development of the disease and of human immunity to it.
September 12, 2002
A TIGR comparison of the whole genomes of two strains of the bacterium that causes tuberculosis has found a surprising number of differences, indicating that genetic variation may be more extensive among Mycobacterium tuberculosis isolates than previously thought, and may play an important role in the development of the disease and of human immunity to it.
The study, led by TIGR investigator Rob Fleischmann, Ph.D., helps lay the groundwork for more comprehensive identification and study of genetic and phenotypic traits in the pathogen, which could in turn help identify better targets for tuberculosis vaccines and theraputic drugs to treat the disease.
"A vaccine or theraputic drug needs to be effective across many strains of tuberculosis," said Fleischmann. "This study and subsequent research will help identify genetic targets that appear in a wide range of M. tuberculosis strains."
Tuberculosis, which kills more than 2 million people a year, has been on the rise lately in many countries, in part because new strains of the pathogen have emerged that are resistant to the drugs that are normally used to treat the disease. The World Health Organization has warned that, unless new treatments are developed and health services are strengthened in developing nations, tuberculosis could infect as many as 1 billion people between 2002 and 2020, causing as many as 36 million deaths.
As part of the research project, TIGR scientists sequenced the whole genome of the M. tuberculosis clinical strain CDC1551 and compared it to the previously-sequenced genome of the laboratory strain H37Rv. Then the researchers examined the genomes to identify genetic variations that may relate to the disease's development, human immunity to it, and the evolution of the strains.
After they found more than 1,000 polymorphisms, researchers then tested more than 200 clinical isolates of M. tuberculosis to see if they showed the same genetic variability at the same points in their genome sequences. In addition, they analyzed the evolutionary relationships among those isolates. Scientists believe that a number of the genetic differences might have resulted from natural selection - such as genes that help the microbe develop resistance to theraputic drugs that are used to treat TB.
"These findings indicate that genetic variation in M. tuberculosis arises through a complex evolutionary process that involves recombination or multiple insertion [or] deletion events occuring independently at the same locus," the researchers write in the article.
The TIGR paper was posted online this week and scheduled for publication in the October 2002 issue of the Journal of Bacteriology. The research was supported by the National Institute of Allergy and Infectious Diseases (NIAID), and included co-authors at the Montefiore Medical Center in New York; Celera Genomics in Rockville, MD., the Johns Hopkins University School of Medicine, and the Albert Einstein College of Medicine in New York.