Washington, Nov 22: Researchers have decoded the gene map of a strain of extensively drug-resistant tuberculosis and have identified mutations that may help develop better treatments.

An international collaboration led by researchers in the US and South Africa also sequenced the genome of another dangerous strain called multidrug-resistant TB, as well as tuberculosis bugs, and found a few mutations may explain how the mutant strains evade antibiotics.

"Tuberculosis is a major threat to global public health that demands new approaches to disease diagnosis and treatment. By looking at the genomes of different strains, we can learn how the tuberculosis microbe outwits current drugs and how new drugs might be designed," said Megan Murray, one of the project's principal investigators, an associate member of the Broad Institute of MIT and Harvard and an associate professor at the Harvard School of Public Health.

"Genome information is a powerful tool for understanding the biology of infectious disease, such as tuberculosis. It is important that genomic data be made immediately available, particularly to researchers in areas most heavily burdened by disease," said Eric Lander, founding director of the Broad Institute of Harvard and MIT.

Tuberculosis, or TB, is a disease caused by a bacteria called Mycobacterium tuberculosis. It infects up to 2 billion people, one-third of the world's population, although most have latent, or inactive infections.

The microbe can mutate and now an estimated 500,000 people globally have multidrug-resistant, or MDR TB, according to the World Health Organization. Standard antibiotics do not affect MDR TB, and patients need special drugs. Extensively drug resistant TB, XDR TB for short, is virtually immune to traditional antibiotics and kills up to 85 percent of those infected.

To shed light on the genetic changes that mediate drug resistance, an international team of scientists undertook a large-scale effort to sequence the genomes of drug sensitive, MDR, and XDR TB isolates of a strain responsible for the current XDR-TB epidemic in KwaZulu-Natal, South Africa. This strain corresponds to one found in patients in Tugela Ferry, a rural town in KwaZulu-Natal that has recently experienced a severe outbreak of XDR TB among patients infected with the human immunodeficiency virus (HIV).

The draft genome sequences of the various TB strains each cover roughly 95 percent of the M. tuberculosis genome. Comparing the DNA sequences in these regions allows the researchers to pinpoint the key differences among them, shedding light on the genetic factors that contribute to TB drug resistance. Strikingly, comparisons of the draft sequences reveal surprisingly few genetic differences among the drug sensitive, MDR and XDR strains: there are only a few dozen small DNA changes.

"That a limited set of genetic differences separates one TB strain from another is important. With the analysis of additional XDR strains, it should be feasible to systematically unravel the biological significance of each genetic variation,” said James Galagan, the associate director of microbial genome analysis at the Broad Institute.

"These results also lay the groundwork for the development of a rapid diagnostic test for TB. Such a test would enable more rapid and accurate diagnoses, and help to prevent the spread of TB - especially the most virulent strains," said Murray.

A significant fraction of the new TB research was accomplished through the use of a powerful new technology for decoding DNA. That approach, based on the principle of single-molecule sequencing, makes it possible to read hundreds of millions of DNA letters simultaneously.

"New technologies for sequencing DNA can accelerate the pace of genomic research, particularly for infectious disease.It is important that these technologies also be made available to researchers in the field, where they are needed most," said Bruce Birren, director of the Microbial Sequencing Center at the Broad Institute. (ANI)