Turbine enzyme’s structure in the crosshairs to target tuberculosis

Tuberculosis (TB) is the deadliest infectious disease worldwide, killing at least 1.5 million people yearly (1). An increasing challenge has been to treat multidrug-resistant (MDR) and extensively drug resistant (XDR) TB cases (MDR-TB and XDR-TB, respectively), estimated at 0.5 million in 2017. This has required up to 2 y of treatment with drugs that can have harsh side effects. Of the estimated people infected with drug-resistant TB, 10,000-fold selectivity for inhibiting the mycobacterial enzyme vs. the mitochondrial enzyme (8). However, this exquisite selectivity made BDQ ineffective against other genera of pathogenic bacteria (3). Modified diarylquinolines can kill gram-positive bacteria like Staphylococcus aureus [the cause of methicillin-resistant S. aureus (MRSA) infections], but reduce the selectivity to just 10-fold vs. the mitochondrial enzyme (9 … [↵][1]1Email: duncant{at}upstate.edu. [1]: #xref-corresp-1-1