Andries, K. et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307, 223–227 (2005).
Sutherland, H. S. et al. 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. Bioorg. Med. Chem. 27, 1292–1307 (2019).
Luo, M. et al. Bedaquiline inhibits the yeast and human mitochondrial ATP synthases. Commun. Biol. 3, 452 (2020).
World Health Organization. Global Tuberculosis Report 2022 (WHO, 2022).
Perveen, S., Kumari, D., Singh, K. & Sharma, R. Tuberculosis drug discovery: progression and future interventions in the wake of emerging resistance. Eur. J. Med. Chem. 229, 114066 (2022).
Munro, S. A. et al. Patient adherence to tuberculosis treatment: a systematic review of qualitative research. PLoS Med. 4, e238 (2007).
Koul, A. et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat. Chem. Biol. 3, 323–324 (2007).
Leibert, E., Danckers, M. & Rom, W. N. New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline. Ther. Clin. Risk Manag. 10, 597–602 (2014).
Pym, A. S. et al. Bedaquiline in the treatment of multidrug-and extensively drug-resistant tuberculosis. Eur. Respir. J. 47, 564–574 (2016).
Chesov, E. et al. Emergence of bedaquiline resistance in a high tuberculosis burden country. Eur. Respir. J. 59, 2100621 (2022).
Guo, H. et al. Structure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline. Nature 589, 143–147 (2021).
Montgomery, M. G., Petri, J., Spikes, T. E. & Walker, J. E. Structure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis. Proc. Natl Acad. Sci. USA 118, e2111899118 (2021).
Preiss, L. et al. Structure of the mycobacterial ATP synthase Fo rotor ring in complex with the anti-TB drug bedaquiline. Sci. Adv. 1, e1500106 (2015).
Courbon, G. M. et al. Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines. EMBO J. 42, e113687 (2023).
Tran, S. L. & Cook, G. M. The F1Fo-ATP synthase of Mycobacterium smegmatis is essential for growth. J. Bacteriol. 187, 5023–5028 (2005).
Gong, H. et al. An electron transfer path connects subunits of a mycobacterial respiratory supercomplex. Science 362, eaat8923 (2018).
Haagsma, A. C., Driessen, N. N., Hahn, M.-M., Lill, H. & Bald, D. ATP synthase in slow-and fast-growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction. FEMS Microbiol. Lett. 313, 68–74 (2010).
Harikishore, A. et al. Mutational analysis of mycobacterial F-ATP synthase subunit δ leads to a potent δ enzyme inhibitor. ACS Chem. Biol. 17, 529–535 (2022).
Tantry, S. J. et al. Discovery of imidazo [1,2-a]pyridine ethers and squaramides as selective and potent inhibitors of mycobacterial adenosine triphosphate (ATP) synthesis. J. Med. Chem. 60, 1379–1399 (2017).
Wong, C. F. et al. A systematic assessment of mycobacterial F1‐ATPase subunit ε’s role in latent ATPase hydrolysis. FEBS J. 288, 818–836 (2021).
Hotra, A. et al. Discovery of a novel mycobacterial F‐ATP synthase inhibitor and its potency in combination with diarylquinolines. Angew. Chem. Int. Ed. Engl. 59, 13295–13304 (2020).
Pethe, K. et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat. Med. 19, 1157–1160 (2013).
Zhou, S. et al. Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates. eLife 10, e69418 (2021).
Koul, A. et al. Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism. Nat. Commun. 5, 3369 (2014).
Sassetti, C. M., Boyd, D. H. & Rubin, E. J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48, 77–84 (2003).
Zimenkov, D. V. et al. Examination of bedaquiline-and linezolid-resistant Mycobacterium tuberculosis isolates from the Moscow region. J. Antimicrob. Chemother. 72, 1901–1906 (2017).
Martinez, E. et al. Mutations associated with in vitro resistance to bedaquiline in Mycobacterium tuberculosis isolates in Australia. Tuberculosis 111, 31–34 (2018).
Görbitz, C. H. Hydrogen-bond distances and angles in the structures of amino acids and peptides. Acta Crystallogr. B 45, 390–395 (1989).
Guillemont, J., Meyer, C., Poncelet, A., Bourdrez, X. & Andries, K. Diarylquinolines, synthesis pathways and quantitative structure–activity relationship studies leading to the discovery of TMC207. Future Med. Chem. 3, 1345–1360 (2011).
Lai, Y. et al. Structure of the human ATP synthase. Mol. Cell 83, 2137–2147 (2023).
Vasanthakumar, T. et al. Structural comparison of the vacuolar and Golgi V-ATPases from Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 116, 7272–7277 (2019).
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Rosenthal, P. B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721–745 (2003).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
Laskowski, R. A. & Swindells, M. B. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51, 2778–2786 (2011).