Hyungjin Eoh, DVM, PhD

Despite effective treatment methods, tuberculosis (TB) kills more people than any other infectious disease. TB is difficult to treat because of a small fraction of M. tuberculosis (Mtb) bacteria variant, called persisters, that surviveeven after antibiotic treatment. Persisters are vulnerable to DNA mutations, which can often lead to drug-resistant (DR) mutations. Thus, the eradication of Mtb persisters and subsequent DR-TB infection is extremely difficult. Recently, we showed that Mtb persisters stopped consuming external nutrients and energy synthesis in favor of using a preexisting simple sugar compound called trehalose. This internal trehalose consumption allows Mtb persisters to maintain their metabolism to neutralize antibiotic effects. We will study whether this internal trehalose consumption is a metabolic effort essential for both persister formation and DR-TB viability. The outcome of this research will improve existing DR-TB treatment methods.

Update: We provided evidence that Mycobacterium tuberculosis (Mtb) develops drug resistance (DR) by cyclic formation of drug tolerant persisters. This was proposed by showing that Mtb persisters and DR mutants share a common adaptive strategy, trehalose metabolism remodeling, to survive antibiotic stress. This remodeling also plays a role in determining the virulence and high DR mutation rates of some clinical TB strains. Taken together, inhibition of trehalose metabolism remodeling can synergize the antibiotic effects on extremely virulent and DR-TB strains with conventional TB antibiotics.