Drying process triggers TB mutations and reveals potential drug target

Researchers at Weill Cornell Medicine found that when tuberculosis bacteria dry out in airborne droplets, they activate a DNA repair response that both helps them survive and increases mutations conferring rifampin resistance. Reducing activity of the DNA repair gene Mfd impaired survival of drug-resistant TB bacteria, suggesting a new therapeutic target. The findings indicate that TB transmission is an active evolutionary phase, not just passive spread.

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The research team simulated the drying and rehydration cycle of Mycobacterium tuberculosis in laboratory conditions, revealing that desiccation triggers oxidative stress and subsequent DNA damage within the bacteria. This damage activates a repair program that allows the pathogen to recover once moisture returns, while simultaneously generating mutations—including those that confer resistance to rifampin, a drug that normally shortens treatment to four to six months.

The study also identified the DNA repair gene Mfd as a potential therapeutic vulnerability. When researchers reduced Mfd activity, drug-resistant tuberculosis bacteria showed impaired survival. Given that tuberculosis affects nearly 11 million people annually and causes roughly 1.2 million