New antibiotic to combat drug-resistant TB found in soil, study finds

Washington: An antibiotic found in soil may help treat drug-resistant tuberculosis (TB) by destroying the mutant bacteria responsible for the disease, a study claims.

For decades, doctors have been using antibiotics to fight tuberculosis, said researchers from Rockefeller University in the US.

Consistently, the microbe responsible for the disease, Mycobacterium tuberculosis, has been fighting back, they said.

When confronted with current drugs, such as the antibiotic rifamycin, the bacterium often mutates in ways that make it resistant to the treatment.

Rates of rifamycin resistance are steadily rising, which presents a major problem to doctors attempting to treat TB.

The study, published in the journal Nature Communications, suggests that an antibiotic found in dirt can destroy mutant mycobacteria.

Rifamycin, or Rif, works by targeting RNA polymerase (RNAP), an enzyme crucial to bacteria's survival.

Resistance develops when the genes coding for RNAP mutate: Even a small genetic change can prevent Rif from binding to the enzyme and obstructing its function.

To circumvent resistance, researchers needed a drug that acted like Rif, but that could bind to RNAP, even in the presence of mutations.

"Rifamycin is naturally produced by a bacterium. So I wanted to find out whether nature had also made Rif analogues -- molecules that look like rifamycin, but that have slight differences," said Sean F Brady, a professor at Rockefeller University.

To identify any such analogues, Brady's lab sequenced the genes of microbes found in soil samples collected from locations across the country.

They hoped to uncover antibiotics that were genetically related to Rif, but with small variations that allowed them to bind to mutated RNAPs.

Through their soil probes, the researchers discovered a group of natural antibiotics, known as kanglemycins, or kangs, that share most of their genes with rifamycin. Analyses by postdoctoral associate James Peek revealed that these antibiotics are capable of combatting bacteria that don't respond to Rif.

Brady hypothesises that kangs might have emerged in response to evolutionary pressures that mirror those present in hospitals. In a clinical setting, bacteria react to antibiotic onslaught by evolving protective mutations.

In turn, researchers create more powerful antibiotics; and, over time, bacteria develop further mutations to evade these new attacks.

In nature, Brady postulates, bacteria and antibiotics may engage in a similar arms race. Bacteria in dirt compete with one another.

One way for a bacterial species to take out the competition is to produce toxins, like Rif, which act as natural antibiotics, researchers said.

Like bacteria in hospitals, bacteria in soil respond to such threats by mutating in ways that confer resistance to the toxins, they said.

However, in time, their rival bacteria might also mutate, producing yet stronger antibiotics. Kangs may be the result of this kind of competition, said Brady.

"It's possible that natural antibiotics are under the same selective pressure that we're putting antibiotics under in the clinic," he said.