Airborne tuberculosis bacteria may mutate as they dry, revealing a target to curb drug resistance

Tuberculosis bacteria released into the air from infected individuals can dry out, forming infectious particles that are highly contagious. Researchers at Weill Cornell Medicine have discovered mechanisms that enable these bacteria to survive drying and develop mutations linked to antibiotic resistance. This suggests that tuberculosis transmission involves more than just the passive movement of bacteria between people and may be a period during which the pathogen evolves.

Tuberculosis, caused by Mycobacterium tuberculosis, affects millions of people and kills hundreds of thousands annually. The study, published in Nature Microbiology, found that desiccation triggers a DNA repair response in tuberculosis bacteria, promoting their survival and increasing the occurrence of mutations that confer resistance to the antibiotic rifampin.

The researchers identified a potential new drug target—reducing the activity of a DNA repair gene called Mfd can impair the survival of drug-resistant tuberculosis bacteria. By mimicking conditions that cause TB bacteria to dry and rehydrate in the laboratory, the team demonstrated that desiccation induces oxidative stress and DNA damage, prompting the bacteria to activate a DNA repair program.

This suggests that tuberculosis has evolved specific mechanisms to withstand the stresses of airborne transmission. Mutations play a critical role in bacterial evolution, and DNA damage during transmission could contribute to the genetic diversity that enables tuberculosis to adapt and acquire drug resistance. Rifampin is a key treatment for tuberculosis, but resistance to this drug is rising, often requiring longer and more costly treatments.

Silencing the Mfd gene during aerosolization experiments reduced the survival of rifampin-resistant tuberculosis bacteria, providing a potential approach to prevent the emergence of rifampin resistance. The findings reveal new insights into the transmission stage of tuberculosis life cycle, offering opportunities for designing effective strategies to interrupt transmission and combat drug resistance.