Tuberculosis kills more than a million people each year. The World Health Organization says it’s the leading cause of death from a single infectious agent — more deadly than HIV/AIDS.
One reason TB is so dangerous is that, out of the 10 million or so infections that arise each year, roughly 500,000 are from drug-resistant Mycobacterium tuberculosis – bacteria immune to physicians’ first, and sometimes second, choice of antibiotics.
M. tuberculosis’ ability to mutate and evolve drug resistance is poorly understood. It’s a problem that naturally interests Dr. Eric Josephs, whose research centers on mutation.
Most organisms use an ancient molecular proofreading mechanism called DNA mismatch repair. As strands of DNA are replicated in the process of cell generation, mismatch repair reads each new string and, if it finds mistakes, fixes them.
“Almost every organism on the planet has the same proofreading mechanism, except for bacteria related to tuberculosis,” says Josephs, an assistant professor at the Joint School of Nanoscience and Nanoengineering. “They appear to have a weird, independently-evolved proofreading mechanism suggestive of mismatch repair. But people don’t know what proteins are involved or how it works.”
Understanding that mechanism, and what turns it off and allows drug resistance to evolve, could one day unlock new treatments for TB and other diseases.