Infectious disease

Cell culture and mouse studies identified an inhibitor of M. tuberculosis cytochrome bc1 that could help treat tuberculosis (TB). Screening of small molecule library in M. tuberculosis culture and chemical synthesis of analogs of a screening hit yielded a morpholino-thiophene-based compound that inhibited bacterial growth with a minimum inhibitory concentration (MIC) of 0.24 μM. In M. tuberculosis growth assays, bacteria expressing mutant cytochrome bc1 had lower sensitivity to the compound than bacteria expressing the wild-type gene, suggesting cytochrome bc1 as the compound’s probable target. In a mouse model of TB, the compound decreased colony forming units (CFUs) in the lungs compared with no treatment. Next steps could include optimizing and testing the inhibitor in additional models of TB...