Posing serious threat to global health, two forms of tuberculosis (TB) have become resistant to rifampicin, regarded the most effective drug against TB, researchers from India and the US say.The two forms are multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Scientists from the two countries have found that a new compound - 24-desmethylrifampicin - has much better anti-bacterial activity than rifampicin against multi-drug-resistant strains of the bacteria that cause TB. This is an important step toward development of new drugs that can transcend antibiotic resistance issues.
"We believe these findings are an important new avenue toward treatment of multi-drug-resistant TB," said Taifo Mahmud, professor at Oregon State University in the US."The approach we are using should be able to create one or more analogs that could help take the place of rifampicin in TB therapy," Mahmud added.A combination of genetic modification and synthetic drug development was used to create the new compound.Further development and testing will be necessary before it is ready for human use, researchers said.
"Drug resistance in rifampicin and related antibiotics has occurred when their bacterial RNA (Ribonucleic acid) polymerase enzymes mutate," Mahmud said, "leaving them largely unaffected by antibiotics that work by inhibiting RNA synthesis."The new approach works by modifying the drug so that it can effectively bind to this mutated enzyme and again achieve its effectiveness."We found out how the antibiotic-producing bacteria make this compound, and then genetically modified that system to remove one part of the backbone of the molecule," Mahmud added.Collaborators on this research were from the University of Delhi and the Institute of Genomics and Integrative Biology in New Delhi.In 1993, resurging levels of TB due to this antibiotic resistance led the World Health Organization to declare it a global health emergency. Today more than a million people around the world are dying each year from TB. After AIDS, it remains the second most common cause of death by infectious disease.The study appeared in the Journal of Biological Chemistry.