Each year, 10 million people contract tuberculosis and 2 million die as a result of the disease. An estimated 2 billion individuals—a third of the world's population—have been exposed to Mycobacterium tuberculosis (MTB) and carry the infection in its latent form, retaining a lifelong risk of developing TB disease.
 
Programs to control tuberculosis now focus on childhood vaccination and treatment for people with active disease. Reversing TB's spread, however, requires an intervention that will prevent disease in those who are already infected. The lack of knowledge about the biology of latent TB infection stands in the way of the development of such an intervention.

Dr. Young is leading an international team of researchers from the U.K., U.S., Singapore, Korea, and Mexico that is attempting to further elucidate the fundamental biology of latency and use this knowledge to develop drugs against latent TB. Their work could also lead to improved treatments for active TB.

The team's central hypothesis is that tuberculosis bacilli persist in tissues in a non-dividing state in which they are relatively tolerant of conventional drugs.

The team’s first objective is to characterize lung tissues from infected individuals. The team hopes to establish an expression profile for persistent bacteria and model the physiology of latent bacilli to assist in predicting drug targets to help ensure latent infections do not develop into active disease.

Investigators are currently testing the effect of metronidazole on active and latent TB lesions in a non-human primate model of disease and have initiated a Phase IIB clinical trial of metronidazole for treatment of drug-resistant TB in Korea. In addition, they have identified maintenance of ATP levels as critical to the survival of non-replicating MTB and are targeting ATP synthesis under hypoxic conditions in ongoing high-throughput whole cell screens.