Drug-resistant tuberculosis is becoming a major threat worldwide. Every year, half a million people are thought to catch strains of TB that are in some way resistant to known antibacterials, with some strains even resistant to multiple drugs. But now research published in Science details how scientists have managed to reverse resistance for one particular drug.

One of the drugs used to treat multi-drug resistant tuberculosis is ethionamide. Yet even this second line of defense is losing its potency, as the bacteria is becoming resistant to this too, increasing the urgency of new treatments. Ethionamide works by being taken up by the TB in an inactive form, where it then interacts with a specific gene in the bacteria known as ethA. This turns the drug into its active form, and results in the death of the TB.

But strains of the disease have emerged in which there is a mutation in ethA, meaning that even when the drug is taken up by the bacteria, it cannot interact with the gene and form the harmful compound. While looking for ways to boost the activity of ethA, which can in turn make the effect of ethionamide more powerful, researchers stumbled upon a new pathway by which TB could activate the drug, which can then be tinkered with.

Usually, this new pathway, which involves a group of genes now called ethA2, is inactive in TB. The scientists have, however, created a compound that effectively turns it on. This would mean that even if the strain of TB has a mutation at the ethA gene, and would therefore ordinarily be resistant to the drug, they could turn on the ethA2 gene complex and make it once again susceptible to ethionamide. According to co-senior author Benoit Déprez, this is like a biological equivalent of malware.

They now stress that the use of this new pathway to tackle ethionamide drug-resistant TB needs to be carefully controlled in order to prevent the disease from developing resistance to this, too. They recommend giving it to patients in pulses to periodically eliminate all the resistant bacteria.

It may also help in another aspect of treating patients who need to take ethionamide. The drug is known to have a significant amount of side effects, including vomit-inducing nausea. It is hoped that this new treatment could therefore be used to cut the amount of the drug used and potentially mitigate some of the side effects.

[H/T: Science Magazine]