Scientists make significant discovery in the fight against drug-resistant tuberculosis

A team of scientists have identified a naturally occurring antibiotic that may help in the fight against drug-resistant Tuberculosis.

Each year, approximately 10 million people fall ill with Tuberculosis (TB) and around 1.7 million die from the devastating disease worldwide.

One of the main antibiotics for TB is rifampicin, however, many strains of the Tuberculosis-causing bacteria – Mycobacterium tuberculosis – have developed resistance to it. Approximately 600,000 people every year are diagnosed with rifampicin-resistant tuberculosis.

Now researchers from Newcastle University and Demuris Ltd have identified that a naturally occurring antibiotic, called kanglemycin A—related to the antibiotic rifampicin—is active against rifampicin-resistant Mycobacterium tuberculosis.

The findings of their study have been published today in the journal, Molecular Cell, and it is hoped that this compound and the enhanced understanding gained from these studies may lead to effective new drug treatments in the future.

Exciting findings

The team used chemical, biophysical, molecular biology and microbiological methods, as well as X-ray crystallography, to show how kanglemycin A binds to its target RNA polymerase and how it manages to overcome resistance.

It was known that rifampicin binds to a groove in the RNA polymerase molecule and that mutations that change the amino-acid sequence of the RNA polymerase can prevent this binding, while maintaining the ability to produce RNA.

Kanglemycin A binds to the same groove, but its structure revealed extensions that also bind just outside the groove allowing it to maintain its affinity to the rifampicin-resistant RNA polymerase and antibiotic activity in rifampicin-resistant bacteria.

Professor Nikolay Zenkin, from Newcastle University’s Institute for Cell and Molecular Biosciences, led the international study.

He said: “Treatment of TB involves a cocktail of antibiotics administered over many months, and resistance to several key antibiotics is becoming a major public health problem around the world.

“Our findings are very exciting and the first step towards developing a new, effective drug treatment for patients with rifampicin resistant TB to prevent fatalities in the future.”

Dr. Michael Hall, from Newcastle University, who led chemical characterization of kanglemycin A, added: “This is an exciting development for the future treatment of rifampicin resistant TB and shows what can be achieved when local businesses and universities work together.”