biostudies-literatureSukheja PHHS | National Institutes of HealthNIAID NIH HHSe02022-16https://www.ebi.ac.uk/biostudies/studies/S-EPMC5312080biostudies-literatureUnknown8(1)Active tuberculosis (TB) and latent <i>Mycobacterium tuberculosis</i> infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating <i>M. tuberculosis</i> "persisters" that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent <i>M. tuberculosis</i> and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors. This screen identified the biphenyl amide GSK1733953A (DG70) as a likely respiration inhibitor. DG70 inhibited both clinical drug-susceptible and drug-resistant <i>M.mBioA Novel Small-Molecule Inhibitor of the <i>Mycobacterium tuberculosis</i> Demethylmenaquinone Methyltransferase MenG Is Bactericidal to Both Growing and Nutritionally Deprived Persister Cells.PMC5312080U19 AI109713R21 AI111647R33 AI1116474R33 AI111647Sukheja PHusain SSoteropoulos PSingleton ELi SGAwasthi DKumar PRusso RBrukh RConnell NPerryman ALAlland DShrestha RFreundlich JSMittal NfalseA Novel Small-Molecule Inhibitor of the <i>Mycobacterium tuberculosis</i> Demethylmenaquinone Methyltransferase MenG Is Bactericidal to Both Growing and Nutritionally Deprived Persister Cells.Active tuberculosis (TB) and latent <i>Mycobacterium tuberculosis</i> infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating <i>M. tuberculosis</i> "persisters" that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent <i>M. tuberculosis</i> and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors. This screen identified the biphenyl amide GSK1733953A (DG70) as a likely respiration inhibitor. DG70 inhibited both clinical drug-susceptible and drug-resistant <i>M.2017-01-01T00:00:00Z2017 Feb2026-06-08T06:17:25.841Z2019-03-27T02:36:40ZS-EPMC53120802819695710.1128/mBio.02022-16