Advances in the design of combination therapies for the treatment of tuberculosis

References

• Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council Tuberculosis Units, 1946-1986, with relevant subsequent publications. Int J Tuberc Lung Dis. 1999;3(10):S231–S279.
   PubMed Web of Science ®Google Scholar
• Kerantzas CA, Jacobs WR. Origins of combination therapy for tuberculosis: lessons for future antimicrobial development and application. mBio. 2017;8(2):e01586–16.
   PubMed Web of Science ®Google Scholar
• Connolly LE, Edelstein PH, Ramakrishnan L. Why is long-term therapy required to cure tuberculosis? PLoS Med. 2007;4(3):e120.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Global tuberculosis report 2020. Geneva: World Health Organization; 2020.
   Google Scholar
• Tiberi S, du Plessis N, Walzl G, et al. Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect Dis. 2018;18(7):e183–e198.
   PubMed Web of Science ®Google Scholar
• Seung KJ, Keshavjee S, Rich ML. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Cold Spring Harb Perspect Med. 2015 Apr 27;5(9):a017863.
   PubMed Web of Science ®Google Scholar
• Dorman SE, Nahid P, Kurbatova EV, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021 May 6;384(18):1705–1718.
   PubMed Web of Science ®Google Scholar
• Conradie F, Diacon AH, Ngubane N, et al., Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893–902. .
   PubMed Web of Science ®Google Scholar
• Riva MA. From milk to rifampicin and back again: history of failures and successes in the treatment for tuberculosis. J Antibiot (Tokyo). 2014;67(9):661–665.
   PubMed Web of Science ®Google Scholar
• Iseman MD. Tuberculosis therapy: past, present and future. Eur Respir J Suppl. 2002 Jul;36(Supplement 36):87s–94s.
   PubMedGoogle Scholar
• Sensi P. History of the development of rifampin. Clin Infect Dis. 1983;5(Supplement_3):S402–S406.
   Google Scholar
• Furin J, Cox H, Pai M. Tuberculosis. Lancet. 2019;393(10181):1642–1656.
   PubMed Web of Science ®Google Scholar
• Pai M, Behr MA, Dowdy D, et al. Tuberculosis. Nat Rev Dis Primers. 2016;2(1):16076.
   PubMed Web of Science ®Google Scholar
• Hunter RL. Pathology of post primary tuberculosis of the lung: an illustrated critical review. Tuberculosis (Edinb). 2011 Nov;91(6):497–509.
   PubMed Web of Science ®Google Scholar
• Orme IM, Basaraba RJ. The formation of the granuloma in tuberculosis infection. Semin Immunol. 2014;26(6):601–609.
   PubMed Web of Science ®Google Scholar
• Yegian D. Biology of tubercle bacilli in necrotic lesions. Am Rev Tuberc. 1952 Nov;66(5):629–631.
   PubMedGoogle Scholar
• Sarathy JP, Dartois V. Caseum: a niche for Mycobacterium tuberculosis drug-tolerant persisters. Clin Microbiol Rev. 2020 Jun 17;33(3). DOI:10.1128/CMR.00159-19.
   PubMed Web of Science ®Google Scholar
• Xie YL, de Jager VR, Chen RY, et al., Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis. Sci Transl Med. 2021;13(579):eabd7618. .
   PubMed Web of Science ®Google Scholar
• Strydom N, Gupta SV, Fox WS, et al. Tuberculosis drugs’ distribution and emergence of resistance in patient’s lung lesions: a mechanistic model and tool for regimen and dose optimization. PLoS Med. 2019 Apr;16(4):e1002773.
   PubMed Web of Science ®Google Scholar
• Ernest JP, Sarathy J, Wang N, et al. Lesion penetration and activity limit the utility of second-line injectable agents in pulmonary tuberculosis. Antimicrob Agents Chemother. 2021Jul12; 65(10). AAC0050621. DOI:10.1128/AAC.00506-21.
   Web of Science ®Google Scholar
• Sarathy J, Blanc L, Alvarez-Cabrera N, et al. Fluoroquinolone Efficacy against tuberculosis is driven by penetration into lesions and activity against resident bacterial populations. Antimicrob Agents Chemother. 2019 May;63(5). DOI:10.1128/AAC.02516-18 .
   Web of Science ®Google Scholar
• Prideaux B, Via LE, Zimmerman MD, et al. The association between sterilizing activity and drug distribution into tuberculosis lesions. Nat Med. 2015;21(10):1223–1227.
   PubMed Web of Science ®Google Scholar
• Sarathy JP, Zuccotto F, Hsinpin H, et al. Prediction of drug penetration in tuberculosis lesions. ACS Infect Dis. 2016;2(8):552–563.
   PubMed Web of Science ®Google Scholar
• Wayne LG, Sohaskey CD. Nonreplicating persistence of Mycobacterium tuberculosis. Annu Rev Microbiol. 2001;55(1):139–163.
   PubMedGoogle Scholar
• Lenaerts A, Barry CE 3rd, Dartois V. Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses. Immunol Rev. 2015 Mar;264(1):288–307.
   PubMed Web of Science ®Google Scholar
• Hoff DR, Ryan GJ, Driver ER, et al. Location of intra- and extracellular M. tuberculosis populations in lungs of mice and Guinea pigs during disease progression and after drug treatment. PLoS One. 2011 Mar 21;6(3):e17550.
   PubMed Web of Science ®Google Scholar
• Lenaerts AJ, Hoff D, Aly S, et al. Location of persisting mycobacteria in a Guinea pig model of tuberculosis revealed by r207910. Antimicrob Agents Chemother. 2007 Sep;51(9):3338–3345.
   PubMed Web of Science ®Google Scholar
• Schrader SM, Vaubourgeix J, Nathan C. Biology of antimicrobial resistance and approaches to combat it. Sci Transl Med. 2020 Jun 24;12(549). DOI:10.1126/scitranslmed.aaz6992.
   PubMed Web of Science ®Google Scholar
• Eoh H, Liu R, Lim J, et al. Central carbon metabolism remodeling as a mechanism to develop drug tolerance and drug resistance in Mycobacterium tuberculosis. Front Cell Infect Microbiol. 2022;12:958240.
   PubMed Web of Science ®Google Scholar
• Iacobino A, Piccaro G, Giannoni F, et al. Fighting tuberculosis by drugs targeting nonreplicating Mycobacterium tuberculosis bacilli. Int J Mycobacteriol. 2017 Jul-Sep;6(3):213–221.
   PubMed Web of Science ®Google Scholar
• Zhang M, Sala C, Dhar N, et al. In vitro and in vivo activities of three oxazolidinones against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2014 Jun;58(6):3217–3223.
   PubMed Web of Science ®Google Scholar
• Raghunandanan S, Jose L, Kumar RA. Dormant Mycobacterium tuberculosis converts isoniazid to the active drug in a Wayne’s model of dormancy. J Antibiot (Tokyo). 2018 Nov;71(11):939–949.
   PubMed Web of Science ®Google Scholar
• Betts JC, Lukey PT, Robb LC, et al. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol. 2002 Feb;43(3):717–731.
   PubMed Web of Science ®Google Scholar
• Wayne LG, Hayes LG. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun. 1996 Jun;64(6):2062–2069.
   PubMed Web of Science ®Google Scholar
• Karakousis PC, Williams EP, Bishai WR. Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis. J Antimicrob Chemother. 2008 Feb;61(2):323–331.
   PubMed Web of Science ®Google Scholar
• Iacobino A, Piccaro G, Giannoni F, et al. Activity of drugs against dormant Mycobacterium tuberculosis. Int J Mycobacteriol. 2016 Dec;5(Suppl 1):S94–S95.
   PubMedGoogle Scholar
• Fattorini L, Piccaro G, Mustazzolu A, et al. Targeting dormant bacilli to fight tuberculosis. Mediterr J Hematol Infect Dis. 2013 Nov 19;5(1):e2013072.
   PubMedGoogle Scholar
• Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005 Jan 14;307(5707):223–227.
   PubMed Web of Science ®Google Scholar
• Singh R, Manjunatha U, Boshoff HI, et al. PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science. 2008 Nov 28;322(5906):1392–1395.
   PubMed Web of Science ®Google Scholar
• Diacon AH, Pym A, Grobusch M, et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009;360(23):2397–2405.
   PubMed Web of Science ®Google Scholar
• Conradie F, Bagdasaryan TR, Borisov S, et al. Bedaquiline–pretomanid–linezolid regimens for drug-resistant tuberculosis. N Engl J Med. 2022;387(9):810–823.
   PubMed Web of Science ®Google Scholar
• Bryk R, Gold B, Venugopal A, et al. Selective killing of nonreplicating mycobacteria. Cell Host Microbe. 2008 Mar 13;3(3):137–145.
   PubMed Web of Science ®Google Scholar
• Darby CM, Nathan CF. Killing of non-replicating Mycobacterium tuberculosis by 8-hydroxyquinoline. J Antimicrob Chemother. 2010;65(7):1424–1427.
   PubMed Web of Science ®Google Scholar
• Grant SS, Kawate T, Nag PP, et al. Identification of novel inhibitors of nonreplicating Mycobacterium tuberculosis using a carbon starvation model. ACS Chem Biol. 2013 Oct 18;8(10):2224–2234.
   PubMed Web of Science ®Google Scholar
• Gold B, Smith R, Nguyen Q, et al. Novel cephalosporins selectively active on nonreplicating Mycobacterium tuberculosis. J Med Chem. 2016;59(13):6027–6044.
   PubMed Web of Science ®Google Scholar
• Chatterjee D, Bonnett SA, Dennison D, et al. A class of hydrazones are active against non-replicating Mycobacterium tuberculosis. PLoS One. 2018;13(10). DOI:10.1371/journal.pone.0196348.
   Web of Science ®Google Scholar
• Neyrolles O, Flint L, Korkegian A, et al. InhA inhibitors have activity against non-replicating Mycobacterium tuberculosis. PLoS One. 2020;15(11):e0239354.
   PubMed Web of Science ®Google Scholar
• Balaban NQ, Helaine S, Lewis K, et al. Definitions and guidelines for research on antibiotic persistence. Nature Rev Microbiol. 2019;17(7):441–448.
   PubMed Web of Science ®Google Scholar
• Aldridge BB, Fernandez-Suarez M, Heller D, et al. Asymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibility. Science. 2012 Jan 6;335(6064):100–104.
   PubMed Web of Science ®Google Scholar
• Schrader SM, Botella H, Jansen R, et al. Multiform antimicrobial resistance from a metabolic mutation. Sci Adv. 2021 Aug;7(35). doi:10.1126/sciadv.abh2037.
   PubMed Web of Science ®Google Scholar
• Levin-Reisman I, Ronin I, Gefen O, et al. Antibiotic tolerance facilitates the evolution of resistance. Science. 2017 Feb 24;355(6327):826–830.
   PubMed Web of Science ®Google Scholar
• Liu J, Gefen O, Ronin I, et al. Effect of tolerance on the evolution of antibiotic resistance under drug combinations. Science. 2020 Jan 10;367(6474):200–204.
   PubMed Web of Science ®Google Scholar
• McGrath M, Gey van Pittius NC, van Helden PD, et al. Mutation rate and the emergence of drug resistance in Mycobacterium tuberculosis. J Antimicrob Chemother. 2014 Feb;69(2):292–302.
   PubMed Web of Science ®Google Scholar
• Ford CB, Shah RR, Maeda MK, et al. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat Genet. 2013 Jul;45(7):784–790.
   PubMed Web of Science ®Google Scholar
• Coelho T, Machado D, Couto I, et al. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil. Front Microbiol. 2015;6:330.
   PubMed Web of Science ®Google Scholar
• Laws M, Jin P, Rahman KM. Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance. Trends Microbiol. 2022;30(1):57–68.
   PubMed Web of Science ®Google Scholar
• Pyle MM. Relative numbers of resistant tubercle bacilli in sputa of patients before and during treatment with streptomycin. Proc Staff Meet Mayo Clin. 1947 Oct 15;22(21):465–473.
   PubMed Web of Science ®Google Scholar
• Palaci M, Dietze R, Hadad DJ, et al. Cavitary disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J Clin Microbiol. 2007 Dec;45(12):4064–4066.
   PubMed Web of Science ®Google Scholar
• British Medical Journal. Streptomycin treatment of pulmonary tuberculosis: a medical research council investigation. Bmj. 1948;2(4582):769–782.
   PubMedGoogle Scholar
• British Medical Journal. Streptomycin in pulmonary tuberculosis. Bmj. 1948;2(4582):790–791.
   PubMedGoogle Scholar
• Bahuguna A, Rawat DS. An overview of new antitubercular drugs, drug candidates, and their targets. Med Res Rev. 2020 Jan;40(1):263–292.
   PubMed Web of Science ®Google Scholar
• Campanico A, Moreira R, Lopes F. Drug discovery in tuberculosis. New drug targets and antimycobacterial agents. Eur J Med Chem. 2018 Apr 25;150:525–545. DOI:10.1016/j.ejmech.2018.03.020.
   PubMed Web of Science ®Google Scholar
• Working Group on New TB Drugs. Compounds | Working Group for New TB Drugs. 2022. [November 22, 2022]. Available from: https://www.newtbdrugs.org/pipeline/compounds
   Google Scholar
• Nuermberger E, Tyagi S, Tasneen R, et al. Powerful bactericidal and sterilizing activity of a regimen containing PA-824, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. Antimicrob Agents Chemother. 2008;52(4):1522–1524.
   PubMed Web of Science ®Google Scholar
• Tasneen R, Li SY, Peloquin CA, et al. Sterilizing activity of novel TMC207- and PA-824-containing regimens in a murine model of tuberculosis. Antimicrob Agents Chemother. 2011 Dec;55(12):5485–5492.
   PubMed Web of Science ®Google Scholar
• Tasneen R, Williams K, Amoabeng O, et al. Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis. Antimicrob Agents Chemother. 2015 Jan;59(1):129–135.
   PubMed Web of Science ®Google Scholar
• Tweed CD, Wills GH, Crook AM, et al. A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB. Int J Tuberc Lung Dis. 2021 Apr 1;25(4):305–314.
   PubMed Web of Science ®Google Scholar
• Global Alliance for TB Drug Development. Trial to evaluate the efficacy, safety and tolerability of BPaMZ in Drug-Sensitive (DS-TB) adult patients and drug-resistant (DR-TB) adult patients: global alliance for TB drug development. 2020. [updated April 30]. Available from: https://ClinicalTrials.gov/show/NCT03338621
   Google Scholar
• University College L, National University Hospital S, Institute SCR. Two-month regimens using novel combinations to augment treatment effectiveness for drug-sensitive tuberculosis. 2018. [updated March 21]. https://ClinicalTrials.gov/show/NCT03474198
   Google Scholar
• Williams K, Minkowski A, Amoabeng O, et al. Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother. 2012 Jun;56(6):3114–3120.
   PubMed Web of Science ®Google Scholar
• Tasneen R, Betoudji F, Tyagi S, et al. Contribution of oxazolidinones to the efficacy of novel regimens containing bedaquiline and pretomanid in a mouse model of tuberculosis. Antimicrob Agents Chemother. 2016 Jan;60(1):270–277.
   PubMed Web of Science ®Google Scholar
• Li SY, Tasneen R, Tyagi S, et al. Bactericidal and sterilizing activity of a novel regimen with bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. Antimicrob Agents Chemother. 2017 Sep;61(9). doi:10.1128/AAC.00913-17.
   Web of Science ®Google Scholar
• Zhang X, Falagas ME, Vardakas KZ, et al. Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. J Thorac Dis. 2015 Apr;7(4):603–615.
   PubMed Web of Science ®Google Scholar
• Dorman SE, Goldberg S, Stout JE, et al. Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium. J Infect Dis. 2012 Oct 1;206(7):1030–1040.
   PubMed Web of Science ®Google Scholar
• Jindani A, Harrison TS, Nunn AJ, et al. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014;371(17):1599–1608.
   PubMed Web of Science ®Google Scholar
• Gillespie SH, Crook AM, McHugh TD, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1577–1587.
   PubMed Web of Science ®Google Scholar
• Andries K, Gevers T, Lounis N. Bactericidal potencies of new regimens are not predictive of their sterilizing potencies in a murine model of tuberculosis. Antimicrob Agents Chemother. 2010 Nov;54(11):4540–4544.
   PubMed Web of Science ®Google Scholar
• Clemens DL, Lee BY, Silva A, et al. Artificial intelligence enabled parabolic response surface platform identifies ultra-rapid near-universal TB drug treatment regimens comprising approved drugs. PLoS One. 2019;14(5):e0215607.
   PubMed Web of Science ®Google Scholar
• De Groote MA, Gilliland JC, Wells CL, et al. Comparative studies evaluating mouse models used for efficacy testing of experimental drugs against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2011 Mar;55(3):1237–1247.
   PubMed Web of Science ®Google Scholar
• Harper J, Skerry C, Davis SL, et al. Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. J Infect Dis. 2012 Feb 15;205(4):595–602.
   PubMed Web of Science ®Google Scholar
• Li SY, Irwin SM, Converse PJ, et al. Evaluation of moxifloxacin-containing regimens in pathologically distinct murine tuberculosis models. Antimicrob Agents Chemother. 2015 Jul;59(7):4026–4030.
   PubMed Web of Science ®Google Scholar
• Mourik BC, Svensson RJ, de Knegt GJ, et al. Improving treatment outcome assessment in a mouse tuberculosis model. Sci Rep. 2018 Apr 9;8(1):5714.
   PubMedGoogle Scholar
• Nuermberger E. Using animal models to develop new treatments for tuberculosis. Semin Respir Crit Care Med. 2008 Oct;29(5):542–551.
   PubMed Web of Science ®Google Scholar
• Nuermberger EL, Yoshimatsu T, Tyagi S, et al. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med. 2004 Feb 1;169(3):421–426.
   PubMed Web of Science ®Google Scholar
• Rosenthal IM, Zhang M, Almeida D, et al. Isoniazid or moxifloxacin in rifapentine-based regimens for experimental tuberculosis? Am J Respir Crit Care Med. 2008 Nov 1;178(9):989–993.
   PubMed Web of Science ®Google Scholar
• Nuermberger EL, Jacobs Jr. WR, McShane H. Preclinical efficacy testing of new drug candidates. Microbiol Spectr. 2017;5(3). DOI:10.1128/microbiolspec.TBTB2-0034-2017
   PubMed Web of Science ®Google Scholar
• Yang H-J, Wang D, Wen X, et al. One size fits all? Not in in vivo modeling of tuberculosis chemotherapeutics. Front Cell Infect Microbiol. 2021;11:613149.
   PubMed Web of Science ®Google Scholar
• Gumbo T, Lenaerts AJ, Hanna D, et al. Nonclinical models for antituberculosis drug development: a landscape analysis. J Infect Dis. 2015;211(suppl_3):S83–S95.
   PubMedGoogle Scholar
• Dharmadhikari AS, Nardell EA. What animal models teach humans about tuberculosis. Am J Respir Cell Mol Biol. 2008 Nov;39(5):503–508.
   PubMed Web of Science ®Google Scholar
• Singh AK, Gupta UD. Animal models of tuberculosis: lesson learnt. Indian J Med Res. 2018 May;147(5):456–463.
   PubMedGoogle Scholar
• Kramnik I, Beamer G. Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies. Semin Immunopathol. 2016 Mar;38(2):221–237.
   PubMed Web of Science ®Google Scholar
• Franzblau SG, DeGroote MA, Cho SH, et al. Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis. Tuberculosis. 2012;92(6):453–488.
   PubMed Web of Science ®Google Scholar
• Grosset J. The sterilizing value of rifampicin and pyrazinamide in experimental short-course chemotherapy. Bull Int Union Tuberc. 1978 Mar;53(1):5–12.
   PubMedGoogle Scholar
• Xu J, Li SY, Almeida DV, et al. Contribution of pretomanid to novel regimens containing bedaquiline with either linezolid or moxifloxacin and pyrazinamide in murine models of tuberculosis. Antimicrob Agents Chemother. 2019 May;63(5). doi:10.1128/AAC.00021-19.
   Web of Science ®Google Scholar
• Lanoix JP, Betoudji F, Nuermberger E. Sterilizing activity of pyrazinamide in combination with first-line drugs in a C3HeB/FeJ mouse model of tuberculosis. Antimicrob Agents Chemother. 2016 Feb;60(2):1091–1096.
   PubMed Web of Science ®Google Scholar
• Lanoix JP, Lenaerts AJ, Nuermberger EL. Heterogeneous disease progression and treatment response in a C3HeB/FeJ mouse model of tuberculosis. Dis Model Mech. 2015 Jun;8(6):603–610.
   PubMed Web of Science ®Google Scholar
• Lee BY, Clemens DL, Silva A, et al. Ultra-rapid near universal TB drug regimen identified via parabolic response surface platform cures mice of both conventional and high susceptibility. PLoS One. 2018;13(11):e0207469.
   PubMed Web of Science ®Google Scholar
• Saini V, Ammerman NC, Chang YS, et al. Treatment-shortening effect of a novel regimen combining clofazimine and high-dose rifapentine in pathologically distinct mouse models of tuberculosis. Antimicrob Agents Chemother. 2019 Jun;63(6). doi:10.1128/AAC.00388-19.
   Web of Science ®Google Scholar
• Chatterji M, Shandil R, Manjunatha MR, et al. 1,4-azaindole, a potential drug candidate for treatment of tuberculosis. Antimicrob Agents Chemother. 2014;58(9):5325–5331.
   PubMed Web of Science ®Google Scholar
• Dartois V. The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells. Nat Rev Microbiol. 2014 Mar;12(3):159–167.
   PubMed Web of Science ®Google Scholar
• Irwin SM, Prideaux B, Lyon ER, et al. Bedaquiline and pyrazinamide treatment responses are affected by pulmonary lesion heterogeneity in Mycobacterium tuberculosis infected C3HeB/FeJ mice. ACS Infect Dis. 2016 Apr 8;2(4):251–267.
   PubMed Web of Science ®Google Scholar
• Liu Y, Tan S, Huang L, et al. Immune activation of the host cell induces drug tolerance in Mycobacterium tuberculosis both in vitro and in vivo. J Exp Med. 2016 May 2;213(5):809–825.
   PubMed Web of Science ®Google Scholar
• Via LE, England K, Weiner DM, et al. A sterilizing tuberculosis treatment regimen is associated with faster clearance of bacteria in cavitary lesions in marmosets. Antimicrob Agents Chemother. 2015;59(7):4181–4189.
   PubMed Web of Science ®Google Scholar
• Winchell CG, Mishra BB, Phuah JY, et al. Evaluation of IL-1 blockade as an adjunct to linezolid therapy for tuberculosis in mice and macaques. Front Immunol. 2020;11:11.
   PubMed Web of Science ®Google Scholar
• Beites T, O’Brien K, Tiwari D, et al. Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development. Nat Commun. 2019 Oct 31;10(1):4970.
   PubMedGoogle Scholar
• Kim S, Scanga CA, Miranda Silva C, et al. Pharmacokinetics of tedizolid, sutezolid, and sutezolid-M1 in non-human primates. Eur J Pharm Sci. 2020;151:105421.
   PubMedGoogle Scholar
• Coleman MT, Chen RY, Lee M, et al. PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis. Sci Transl Med. 2014 Dec 3;6(265):265ra167.
   PubMed Web of Science ®Google Scholar
• Rajoli RKR, Podany AT, Moss DM, et al. Modelling the long-acting administration of anti-tuberculosis agents using PBPK: a proof of concept study. Int J Tuberc Lung Dis. 2018 Aug 1;22(8):937–944.
   PubMed Web of Science ®Google Scholar
• Fors J, Strydom N, Fox WS, et al. Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis. PLoS Comput Biol. 2020 Aug;16(8):e1008107.
   PubMed Web of Science ®Google Scholar
• Pienaar E, Cilfone NA, Lin PL, et al. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment. J Theor Biol. 2015;367:166–179.
   PubMed Web of Science ®Google Scholar
• Bigelow KM, Deitchman AN, S-Y L, et al. Pharmacodynamic correlates of linezolid activity and toxicity in murine models of tuberculosis. J Infect Dis. 2021;223(11):1855–1864.
   PubMed Web of Science ®Google Scholar
• Rifat D, Prideaux B, Savic RM, et al. Pharmacokinetics of rifapentine and rifampin in a rabbit model of tuberculosis and correlation with clinical trial data. Sci Transl Med. 2018;10(435). DOI:10.1126/scitranslmed.aai7786.
   PubMed Web of Science ®Google Scholar
• Lyons MA. Modeling and simulation of pretomanid pharmacodynamics in pulmonary tuberculosis patients. Antimicrob Agents Chemother. 2019 Sep 30;63(12). DOI:10.1128/AAC.00732-19.
   PubMed Web of Science ®Google Scholar
• Lyons MA. Pretomanid dose selection for pulmonary tuberculosis: an application of multi‐objective optimization to dosage regimen design. CPT Pharmacometrics Syst Pharmacol. 2021;10(3):211–219.
   PubMedGoogle Scholar
• Gumbo T, Alffenaar JC. Pharmacokinetic/pharmacodynamic background and methods and scientific evidence base for dosing of second-line tuberculosis drugs. Clin Infect Dis. 2018 Nov 28;67(suppl_3):S267–S273.
   PubMedGoogle Scholar
• Gumbo T, Pasipanodya JG, Romero K, et al. Forecasting accuracy of the hollow fiber model of tuberculosis for clinical therapeutic outcomes. Clin Infect Dis. 2015 Aug 15;61 Suppl 1(suppl 1):S25–31.
   PubMedGoogle Scholar
• Humphries H, Almond L, Berg A, et al. Development of physiologically-based pharmacokinetic models for standard of care and newer tuberculosis drugs. CPT Pharmacometrics Syst Pharmacol. 2021 Nov;10(11):1382–1395.
   PubMedGoogle Scholar
• Riccardi N, Canetti D, Rodari P, et al. Tuberculosis and pharmacological interactions: a narrative review. Curr Res Pharmacol Drug Discov. 2021;2:100007.
   PubMedGoogle Scholar
• Alffenaar JC, Gumbo T, Dooley KE, et al. Integrating pharmacokinetics and pharmacodynamics in operational research to end tuberculosis. Clin Infect Dis. 2020 Apr 10;70(8):1774–1780.
   PubMed Web of Science ®Google Scholar
• Garcia-Cremades M, Solans BP, Strydom N, et al. Emerging therapeutics, technologies, and drug development strategies to address patient nonadherence and improve tuberculosis treatment. Annu Rev Pharmacol Toxicol. 2022 Jan 6;62(1):197–210.
   PubMedGoogle Scholar
• Marino S, Kirschner DE. A multi-compartment hybrid computational model predicts key roles for dendritic cells in tuberculosis infection. Computation (Basel). 2016;4(4). DOI: 10.3390/computation4040039.
   PubMedGoogle Scholar
• Warsinske HC, Pienaar E, Linderman JJ, et al. Deletion of TGF-beta1 increases bacterial clearance by cytotoxic T cells in a tuberculosis granuloma model. Front Immunol. 2017;8:1843.
   PubMed Web of Science ®Google Scholar
• Pienaar E, Sarathy J, Prideaux B, et al. Comparing efficacies of moxifloxacin, levofloxacin and gatifloxacin in tuberculosis granulomas using a multi-scale systems pharmacology approach. PLoS Comput Biol. 2017 Aug;13(8):e1005650.
   PubMed Web of Science ®Google Scholar
• Marino S, Hult C, Wolberg P, et al. The role of dimensionality in understanding granuloma formation. Computation (Basel). 2018 Dec;6(4). doi:10.3390/computation6040058
   PubMedGoogle Scholar
• Hult C, Mattila JT, Gideon HP, et al. Neutrophil dynamics affect Mycobacterium tuberculosis granuloma outcomes and dissemination. Front Immunol. 2021;12:712457.
   PubMed Web of Science ®Google Scholar
• Cicchese JM, Sambarey A, Kirschner D, et al. A multi-scale pipeline linking drug transcriptomics with pharmacokinetics predicts in vivo interactions of tuberculosis drugs. Sci Rep. 2021 Mar 11;11(1):5643.
   PubMed Web of Science ®Google Scholar
• Gumbo T, Pasipanodya JG, Nuermberger E, et al. Correlations between the hollow fiber model of tuberculosis and therapeutic events in tuberculosis patients: learn and confirm. Clin Infect Dis. 2015 Aug 15;61 Suppl 1(suppl 1):S18–24.
   PubMedGoogle Scholar
• Parish T. In vitro drug discovery models for Mycobacterium tuberculosis relevant for host infection. Expert Opin Drug Discov. 2020 Mar;15(3):349–358.
   PubMed Web of Science ®Google Scholar
• Dartois VA, Rubin EJ. Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat Rev Microbiol. 2022 Apr 27;20(11):685–701.
   PubMed Web of Science ®Google Scholar
• Russell DG, VanderVen BC, Lee W, et al. Mycobacterium tuberculosis wears what it eats. Cell Host Microbe. 2010 Jul 22;8(1):68–76.
   PubMed Web of Science ®Google Scholar
• VanderVen BC, Fahey RJ, Lee W, et al. Novel inhibitors of cholesterol degradation in Mycobacterium tuberculosis reveal how the bacterium’s metabolism is constrained by the intracellular environment. PLoS Pathog. 2015 Feb;11(2):e1004679.
   PubMed Web of Science ®Google Scholar
• Griffin JE, Pandey AK, Gilmore SA, et al. Cholesterol catabolism by Mycobacterium tuberculosis requires transcriptional and metabolic adaptations. Chem Biol. 2012 Feb 24;19(2):218–227.
   PubMedGoogle Scholar
• Guerrini V, Prideaux B, Blanc L, et al. Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific. PLoS Pathog. 2018 Aug;14(8):e1007223.
   PubMedGoogle Scholar
• Lee W, VanderVen BC, Fahey RJ, et al. Intracellular Mycobacterium tuberculosis exploits host-derived fatty acids to limit metabolic stress. J Biol Chem. 2013 Mar 8;288(10):6788–6800.
   PubMed Web of Science ®Google Scholar
• Lovewell RR, Sassetti CM, VanderVen BC. Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection. Curr Opin Microbiol. 2016 Feb;29:30–36.
   PubMed Web of Science ®Google Scholar
• Wilburn KM, Fieweger RA, VanderVen BC. Cholesterol and fatty acids grease the wheels of Mycobacterium tuberculosis pathogenesis. Pathog Dis. 2018 Mar 1;76(2). DOI:10.1093/femspd/fty021.
   PubMed Web of Science ®Google Scholar
• Miner MD, Chang JC, Pandey AK, et al. Role of cholesterol in Mycobacterium tuberculosis infection. Indian J Exp Biol. 2009 Jun;47(6):407–411.
   PubMed Web of Science ®Google Scholar
• Baker JJ, Dechow SJ, Abramovitch RB. Acid fasting: modulation of Mycobacterium tuberculosis metabolism at acidic pH. Trends Microbiol. 2019 Nov;27(11):942–953.
   PubMed Web of Science ®Google Scholar
• Tarshis MS, Weed WA Jr. Lack of significant in vitro sensitivity of Mycobacterium tuberculosis to pyrazinamide on three different solid media. Am Rev Tuberc. 1953 Mar;67(3):391–395.
   PubMedGoogle Scholar
• McDermott W, Tompsett R. Activation of pyrazinamide and nicotinamide in acidic environments in vitro. Am Rev Tuberc. 1954 Oct;70(4):748–754.
   PubMedGoogle Scholar
• Lamont EA, Dillon NA, Baughn AD. The bewildering antitubercular action of pyrazinamide. Microbiol Mol Biol Rev. 2020 May 20;84(2). DOI:10.1128/MMBR.00070-19.
   PubMed Web of Science ®Google Scholar
• Daniel J, Maamar H, Deb C, et al. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages. PLoS Pathog. 2011 Jun;7(6):e1002093.
   PubMed Web of Science ®Google Scholar
• Guirado E, Schlesinger LS, Kaplan G. Macrophages in tuberculosis: friend or foe. Semin Immunopathol. 2013 Sep;35(5):563–583.
   PubMed Web of Science ®Google Scholar
• Giraud-Gatineau A, Coya JM, Maure A, et al. The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection. Elife. 2020 May 4;9. DOI:10.7554/eLife.55692
   PubMed Web of Science ®Google Scholar
• Cole ST. Inhibiting Mycobacterium tuberculosis within and without. Philos Trans R Soc Lond B Biol Sci. 2016 Nov 5;371(1707):20150506.
   PubMed Web of Science ®Google Scholar
• Urtti A, Baik J, Rosania GR. Macrophages sequester clofazimine in an intracellular liquid crystal-like supramolecular organization. PLoS ONE. 2012;7(10). DOI:10.1371/journal.pone.0041410
   PubMed Web of Science ®Google Scholar
• Greenwood DJ, Dos Santos MS, Huang S, et al. Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages. Science. 2019 Jun 28;364(6447):1279–1282.
   PubMed Web of Science ®Google Scholar
• Silva A, Lee B-Y, Clemens DL, et al. Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model. Proc Nat Acad Sci. 2016;113(15):E2172–E2179.
   PubMed Web of Science ®Google Scholar
• Horwitz MA, Clemens DL, Lee BY. AI‐enabled parabolic response surface approach identifies ultra short‐course near‐universal TB drug regimens. Adv Ther. 2019;3(4):1900086.
   Google Scholar
• Lee BY, Clemens DL, Silva A, et al. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time. Nat Commun. 2017 Jan 24;8(1):14183.
   PubMedGoogle Scholar
• Lanoix JP, Ioerger T, Ormond A, et al. Selective inactivity of pyrazinamide against tuberculosis in C3HeB/FeJ mice is best explained by neutral pH of caseum. Antimicrob Agents Chemother. 2016 Feb;60(2):735–743.
   PubMed Web of Science ®Google Scholar
• Gold B, Nathan C. Targeting phenotypically tolerant Mycobacterium tuberculosis. Microbiol Spectr. 2017 Jan;5(1). DOI:10.1128/microbiolspec.TBTB2-0031-2016.
   PubMed Web of Science ®Google Scholar
• Gold B, Roberts J, Ling Y, et al. Rapid, semiquantitative assay to discriminate among compounds with activity against replicating or nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Oct;59(10):6521–6538.
   PubMed Web of Science ®Google Scholar
• Gold B, Warrier T, Nathan C. A multi-stress model for high throughput screening against non-replicating Mycobacterium tuberculosis. Methods Mol Biol. 2015;1285:293–315. * Multi. * Multistress model amenable to systematic screening of compounds and combinations.
   PubMedGoogle Scholar
• Wayne LG. Dynamics of submerged growth of Mycobacterium tuberculosis under aerobic and microaerophilic conditions. Am Rev Respir Dis. 1976 Oct;114(4):807–811.
   PubMedGoogle Scholar
• Sohaskey CD. Nitrate enhances the survival of Mycobacterium tuberculosis during inhibition of respiration. J Bacteriol. 2008;190(8):2981–2986.
   PubMed Web of Science ®Google Scholar
• Cunningham-Bussel A, Zhang T, Nathan CF. Nitrite produced by Mycobacterium tuberculosis in human macrophages in physiologic oxygen impacts bacterial ATP consumption and gene expression. Proc Natl Acad Sci U S A. 2013;110(45):E4256–E4265.
   PubMed Web of Science ®Google Scholar
• Larkins-Ford J, Greenstein T, Van N, et al. Systematic measurement of combination-drug landscapes to predict in vivo treatment outcomes for tuberculosis. Cell Syst. 2021 Nov 17;12(11):1046–1063 e7.
   PubMed Web of Science ®Google Scholar
• Deb C, Lee CM, Dubey VS, et al. A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PLoS One. 2009 Jun 29;4(6):e6077.
   PubMed Web of Science ®Google Scholar
• Larkins-Ford J, Degefu YN, Van N, et al. Design principles to assemble drug combinations for effective tuberculosis therapy using interpretable pairwise drug response measurements. Cell Rep Med. 2022 Sep 20;3(9):100737.
   PubMedGoogle Scholar
• Gumbo T, Louie A, Deziel Mark R, et al. Selection of a moxifloxacin dose that suppresses drug resistance in Mycobacterium tuberculosis, by use of an in vitro pharmacodynamic infection model and mathematical modeling. J Infect Dis. 2004;190(9):1642–1651.
   PubMed Web of Science ®Google Scholar
• Cavaleri M, Manolis E. Hollow fiber system model for tuberculosis: the European medicines agency experience. Clin Infect Dis. 2015;61(suppl 1):S1–S4.
   PubMedGoogle Scholar
• Pasipanodya JG, Nuermberger E, Romero K, et al. Systematic analysis of hollow fiber model of tuberculosis experiments. Clin Infect Dis. 2015 Aug 15;61 Suppl 1(suppl 1):S10–7.
   PubMedGoogle Scholar
• Mason AB, Dartois V. Drug sensitivity testing of Mycobacterium tuberculosis growing in a hollow fiber bioreactor. Methods Mol Biol. 2021;2314:715–731.
   PubMedGoogle Scholar
• Stein C, Makarewicz O, Bohnert JA, et al. Three dimensional checkerboard synergy analysis of colistin, meropenem, tigecycline against multidrug-resistant clinical Klebsiella pneumonia isolates. PLoS One. 2015;10(6):e0126479.
   PubMed Web of Science ®Google Scholar
• Cokol M, Kuru N, Bicak E, et al. Efficient measurement and factorization of high-order drug interactions in Mycobacterium tuberculosis. Sci Adv. 2017;3(10):e1701881.
   PubMed Web of Science ®Google Scholar
• Kehe J, Kulesa A, Ortiz A, et al. Massively parallel screening of synthetic microbial communities. Proc Nat Acad Sci. 2019;116(26):12804–12809.
   PubMed Web of Science ®Google Scholar
• Schön T, Köser CU, Werngren J, et al. What is the role of the EUCAST reference method for MIC testing of the Mycobacterium tuberculosis complex? Clin Microbiol Infect. 2020;26(11):1453–1455.
   PubMed Web of Science ®Google Scholar
• Schön T, Werngren J, Machado D, et al. Multicentre testing of the EUCAST broth microdilution reference method for MIC determination on Mycobacterium tuberculosis. Clin Microbiol Infect. 2021;27(2):288.e1–288.e4.
   PubMed Web of Science ®Google Scholar
• Palomino JC, Martin A, Camacho M, et al. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2002 Aug;46(8):2720–2722.
   PubMed Web of Science ®Google Scholar
• Martin A, Camacho M, Portaels F, et al. Resazurin microtiter assay plate testing of Mycobacterium tuberculosis susceptibilities to second-line drugs: rapid, simple, and inexpensive method. Antimicrob Agents Chemother. 2003;47(11):3616–3619.
   PubMed Web of Science ®Google Scholar
• Taneja NK, Tyagi JS. Resazurin reduction assays for screening of anti-tubercular compounds against dormant and actively growing Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis. J Antimicrob Chemother. 2007;60(2):288–293.
   PubMed Web of Science ®Google Scholar
• Queval CJ, Song OR, Delorme V, et al. A microscopic phenotypic assay for the quantification of intracellular mycobacteria adapted for high-throughput/high-content screening. J Vis Exp. 2014 Jan;17(83):e51114.
   Google Scholar
• Stanley SA, Barczak AK, Silvis MR, et al. Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth. PLoS Pathog. 2014 Feb;10(2):e1003946.
   PubMed Web of Science ®Google Scholar
• Sorrentino F, Gonzalez Del Rio R, Zheng X, et al. Development of an intracellular screen for new compounds able to inhibit Mycobacterium tuberculosis growth in human macrophages. Antimicrob Agents Chemother. 2016 Jan;60(1):640–645.
   PubMed Web of Science ®Google Scholar
• Rodrigues Felix C, Gupta R, Geden S, et al. Selective killing of dormant Mycobacterium tuberculosis by marine natural products. Antimicrob Agents Chemother. 2017 Aug;61(8). doi:10.1128/AAC.00743-17.
   PubMed Web of Science ®Google Scholar
• Andreu N, Zelmer A, Fletcher T, et al. Optimisation of bioluminescent reporters for use with mycobacteria. PLoS One. 2010 May 24;5(5):e10777.
   PubMed Web of Science ®Google Scholar
• Early JV, Mullen S, Parish T. A rapid, low pH, nutrient stress, assay to determine the bactericidal activity of compounds against non-replicating Mycobacterium tuberculosis. PLoS One. 2019;14(10):e0222970.
   PubMed Web of Science ®Google Scholar
• Sharma S, Gelman E, Narayan C, et al. Simple and rapid method to determine antimycobacterial potency of compounds by using autoluminescent Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2014 Oct;58(10):5801–5808.
   PubMed Web of Science ®Google Scholar
• Zhang T, Li S-Y, Nuermberger EL. Autoluminescent Mycobacterium tuberculosis for rapid, real-time, non-invasive assessment of drug and vaccine efficacy. PLOS ONE. 2012;7(1):e29774.
   PubMed Web of Science ®Google Scholar
• Walter ND, Born SEM, Robertson GT, et al. Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens. Nat Commun. 2021;12(1). DOI:10.1038/s41467-021-22833-6
   Web of Science ®Google Scholar
• Wayne LG, Sramek HA. Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1994 Sep;38(9):2054–2058.
   PubMed Web of Science ®Google Scholar
• Pethe K, Sequeira PC, Agarwalla S, et al. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat Commun. 2010 Aug 24;1(1):57.
   PubMedGoogle Scholar
• Drusano GL, Kim S, Almoslem M, et al. The funnel: a screening technique for identifying optimal two-drug combination chemotherapy regimens. Antimicrob Agents Chemother. 2021 Jan 20;65(2). doi:10.1128/AAC.02172-20.
   Web of Science ®Google Scholar
• Sarathy JP, Liang HH, Weiner D, et al. An in vitro caseum binding assay that predicts drug penetration in tuberculosis lesions. J Vis Exp. 2017 May;8(123):55559.
   Google Scholar
• Macalino SJY, Billones JB, Organo VG, et al. In silico strategies in tuberculosis drug discovery. Molecules. 2020 Feb 4;25(3):665.
   PubMed Web of Science ®Google Scholar
• Singh R, Ramachandran V, Shandil R, et al. In silico-based high-throughput screen for discovery of novel combinations for tuberculosis treatment. Antimicrob Agents Chemother. 2015;59(9):5664–5674.
   PubMed Web of Science ®Google Scholar
• Srinivas V, Ruiz RA, Pan M, et al. Transcriptome signature of cell viability predicts drug response and drug interaction in Mycobacterium tuberculosis. Cell Rep Methods. 2021 Dec 20;1(8):None.
   PubMedGoogle Scholar
• Rock J, Kline KA. Tuberculosis drug discovery in the CRISPR era. PLoS Pathog. 2019 Sep;15(9):e1007975.
   PubMed Web of Science ®Google Scholar
• Bosch B, DeJesus MA, Poulton NC, et al., Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis. Cell. 2021;184(17):4579–4592.e24. .
   PubMed Web of Science ®Google Scholar
• Johnson EO, LaVerriere E, Office E, et al. Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes. Nature. 2019 Jul;571(7763):72–78.
   PubMed Web of Science ®Google Scholar
• Doran JL, Pang Y, Mdluli KE, et al. Mycobacterium tuberculosis efpA encodes an efflux protein of the QacA transporter family. Clin Diagn Lab Immunol. 1997 Jan;4(1):23–32.
   PubMedGoogle Scholar
• Johnson EO, Office E, Kawate T, et al. Large-scale chemical-genetic strategy enables the design of antimicrobial combination chemotherapy in mycobacteria. ACS Infect Dis. 2020 Jan 10;6(1):56–63.
   PubMed Web of Science ®Google Scholar
• Rai D, Mehra S. The mycobacterial efflux pump EfpA can induce high drug tolerance to many antituberculosis drugs, including moxifloxacin, in Mycobacterium smegmatis. Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0026221.
   PubMed Web of Science ®Google Scholar
• Ma S, Jaipalli S, Larkins-Ford J, et al. Transcriptomic signatures predict regulators of drug synergy and clinical regimen efficacy against tuberculosis. mBio. 2019 Nov 12;10(6). doi:10.1128/mBio.02627-19.
   Web of Science ®Google Scholar
• Aldridge BB, Barros-Aguirre D, Barry CE 3rd, et al. The tuberculosis drug accelerator at year 10: what have we learned? Nat Med. 2021 Aug;27(8):1333–1337.
   PubMed Web of Science ®Google Scholar