Targeting TB persistence

A group of researchers from California and New York has identified a small molecule with activity against currently intractable nonreplicating stages and drug-resistant strains of Mycobacterium tuberculosis.¹ The compound, which works by blocking a cell wall biosynthesis enzyme and a cofactor biosynthesis enzyme, could be combined with existing tuberculosis drugs to help shorten treatment duration and prevent or eliminate the emergence of resistant bacteria.

One of the major challenges of treating TB is bacterial persistence, which occurs when the bacteria enter a dormant, nonreplicating phase. Most marketed drugs are not effective against dormant TB, and new compounds are still mostly screened against growing bacteria, which have different metabolic properties and requirements than latent bacteria and only represent a fraction of the life cycle of M. tuberculosis...