Sequencing the TB Genome Will Lead to Rapid Diagnostic Test

Genomes of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacteria isolates from a recent tuberculosis (TB) outbreak in KwaZulu-Natal, South Africa, were decoded. The DNA sequences will lead to a rapid diagnostic test for TB and help prevent transmission of the disease, especially the virulent form.

Globally, TB is a major cause of infectious disease deaths. Nearly 2 billion people, comprising roughly one third of the world's population, are thought to carry Mycobacterium tuberculosis, the culprit bacterium. Major obstacles to controlling the disease stem from the microbe's ability to evade current treatments, which typically require prolonged use by patients and are often not curative.

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). There, 52 of 53 people infected with this strain died.

The draft genome sequences of the various TB strains each cover roughly 95% of the M. tuberculosis genome. Comparing the DNA sequences in these regions allowed the scientists to pinpoint the key differences among them, shedding light on the genetic factors that contribute to TB drug resistance. Comparisons of the draft sequences revealed few genetic differences among the drug sensitive, MDR and XDR strains: there were only a few dozen small DNA changes.

Some of these differences are located in genes known to be involved in TB drug resistance, while others are found in novel genes, whose roles have not been previously investigated. Some of these genes may represent new drug-resistance genes, while others may simply contain random mutations.

"Tuberculosis is a major threat to global public health that demands new approaches to disease diagnosis and treatment,” said Megan Murray, one of the project's principal investigators, an associate member of the Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard (Cambridge, MA, USA) and associate professor at the Harvard School of Public Health. "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.”

The work was the result of a collaboration between scientists in the Microbial Sequencing Center at the Broad Institute of Harvard, Megan Murray of the Harvard School of Public Health (Boston, MA, USA), and Willem Sturm and colleagues at the Nelson Mandela Medical School (Durban, South Africa). In view of the seriousness of the current situation with regard to drug resistant TB, the scientists immediately shared both the genome sequence and their initial analysis far in advance of submitting a scientific paper to accelerate work on drug-resistant TB around the world.


Related Links:
Microbial Sequencing Center at the Broad Institute of Harvard and MIT
Harvard School of Public Health
Nelson Mandela Medical School