Weill Cornell Study Finds Tuberculosis Bacteria May Mutate as They Dry in Air

Tuberculosis bacteria released into the air by an infected person dry out to form tiny infectious particles that are second only to measles in contagiousness. Weill Cornell Medicine researchers have found specific mechanisms that let the bacteria not only survive this drying process but also generate mutations linked to antibiotic resistance, according to a study published in Nature Microbiology. Tuberculosis, caused by Mycobacterium tuberculosis, affects nearly 11 million people and causes roughly 1.2 million deaths worldwide each year.

By mimicking the drying and rehydration of the bacteria in the lab, the researchers showed that desiccation causes oxidative stress and DNA damage in Mycobacterium tuberculosis, prompting the bacteria to activate a DNA repair program that helps them survive and recover once moisture returns. That same repair response increased the appearance of mutations that made the bacteria resistant to rifampin, a cornerstone tuberculosis drug that helps shorten treatment to about four to six months.

The team also identified a possible new drug target: silencing a DNA repair gene called Mfd during laboratory aerosolization experiments reduced the survival of rifampin-resistant tuberculosis bacteria. Analyzing more than 50,000 tuberculosis genomes from patients worldwide, the researchers found that strains carrying mutations in Mfd were significantly less likely to carry the most common rifampin-resistance mutation, supporting the lab finding that Mfd helps drug-resistant strains survive transmission.

Tuberculosis has evolved the ability to spread efficiently from person to person, said senior author Dr. Kyu Rhee, a professor of medicine and of microbiology and immunology at Weill Cornell. Our findings shed light on this understudied stage of the tuberculosis life cycle and lay the groundwork for new strategies to interrupt transmission and combat drug resistance, he said.