We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×

A review of current and promising nontuberculous mycobacteria antibiotics

    Christophe R Cantelli

    Université de Picardie-Jules-Verne, Agents Infectieux, Résistance et Chimiothérapie, UR 4294, UFR de Pharmacie, 1 Rue des Louvels, F-80037, Amiens Cedex 1, France

    ,
    Alexandra Dassonville-Klimpt

    Université de Picardie-Jules-Verne, Agents Infectieux, Résistance et Chimiothérapie, UR 4294, UFR de Pharmacie, 1 Rue des Louvels, F-80037, Amiens Cedex 1, France

    &
    Pascal Sonnet

    *Author for correspondence:

    E-mail Address: pascal.sonnet@u-picardie.fr

    Université de Picardie-Jules-Verne, Agents Infectieux, Résistance et Chimiothérapie, UR 4294, UFR de Pharmacie, 1 Rue des Louvels, F-80037, Amiens Cedex 1, France

    Published Online:https://doi.org/10.4155/fmc-2021-0048

    Nontuberculous mycobacteria infections are a growing concern, and their incidence has been increasing worldwide in recent years. Current treatments are not necessarily useful because many were initially designed to work against other bacteria, such as Mycobacterium tuberculosis. In addition, inadequate treatment means that resistant strains are increasingly appearing, particularly for Mycobacterium abscessus, one of the most virulent nontuberculous mycobacteria. There is an urgent need to develop new antibiotics specifically directed against these nontuberculous mycobacteria. To help in this fight against the emergence of these pathogens, this review describes the most promising heterocyclic antibiotics under development, with particular attention paid to their structure–activity relationships.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest

    References

    • 1. Tortoli E. Microbiological features and clinical relevance of new species of the genus Mycobacterium. Clin. Microbiol. Rev. 27(4), 727–752 (2014).
    • 2. Bento CM, Gomes MS, Silva T. Looking beyond typical treatments for atypical mycobacteria. Antibiotics (Basel) 9(1), 18 (2020).
    • 3. Haworth CS, Banks J, Capstick T et al. British Thoracic Society guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). BMJ Open Respir. Res. 4(1), e000242 (2017). • Discusses most recent guideline for the treatment of pulmonary infection with nontuberculous mycobacteria (NTMs).
    • 4. Hoefsloot W, van Ingen J, Andrejak C et al. The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study. Eur. Respir. J. 42(6), 1604–1613 (2013).
    • 5. Falkinham JO. Nontuberculous mycobacteria in the environment. Clin. Chest Med. 23(3), 529–551 (2002).
    • 6. Griffith DE, Aksamit T, Brown-Elliott BA et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am. J. Respir. Crit. Care Med. 175(4), 367–416 (2007).
    • 7. Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin. Chest Med. 36(1), 13–34 (2015).
    • 8. Brode SK, Daley CL, Marras TK. The epidemiologic relationship between tuberculosis and non-tuberculous mycobacterial disease: a systematic review. Int. J. Tuberc. Lung Dis. 18(11), 1370–1377 (2014).
    • 9. Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in US Medicare beneficiaries. Am. J. Respir. Crit. Care Med. 185(8), 881–886 (2012).
    • 10. Ripoll F, Pasek S, Schenowitz C et al. Non mycobacterial virulence genes in the genome of the emerging pathogen Mycobacterium abscessus. PLoS ONE 4(6), e5660 (2009).
    • 11. Choo SW, Wee WY, Ngeow YF et al. Genomic reconnaissance of clinical isolates of emerging human pathogen Mycobacterium abscessus reveals high evolutionary potential. Sci. Rep. 4(1), 1–10 (2014).
    • 12. Shahraki AH, Heidarieh P, Bostanabad SZ et al. “Multidrug-resistant tuberculosis” may be nontuberculous mycobacteria. Eur. J. Intern. Med. 26(4), 279–284 (2015).
    • 13. van Ingen J, Boeree MJ, van Soolingen D, Mouton JW. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria. Drug Resist. Updat. 15(3), 149–161 (2012).
    • 14. Dartois V. The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells. Nat. Rev. Microbiol. 12(3), 159–167 (2014).
    • 15. Nessar R, Cambau E, Reyrat JM, Murray A, Gicquel B. Mycobacterium abscessus: a new antibiotic nightmare. J. Antimicrob. Chemother. 67(4), 810–818 (2012).
    • 16. Sahu RK, Singh K, Subodh S. Adverse drug reactions to anti-TB drugs: pharmacogenomics perspective for identification of host genetic markers. Curr. Drug Metab. 16(7), 538–552 (2015).
    • 17. Liu Y, Matsumoto M, Ishida H et al. Delamanid: from discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB). Tuberculosis (Edinb.) 111, 20–30 (2018).
    • 18. Hashizume T, Ishino F, Nakagawa J, Tamaki S, Matsuhashi M. Studies on the mechanism of action of imipenem (N-formimidoylthienamycin) in vitro: binding to the penicillin-binding proteins (PBPs) in Escherichia coli and Pseudomonas aeruginosa, and inhibition of enzyme activities due to the PBPs in E. coli. J. Antibiot. (Tokyo) 37(4), 394–400 (1984).
    • 19. Belanger AE, Besra GS, Ford ME et al. The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc. Natl Acad. Sci. USA 93(21), 11919–11924 (1996).
    • 20. Mikušová K, Huang H, Yagi T et al. Decaprenylphosphoryl arabinofuranose, the donor of the d-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose. J. Bacteriol. 187(23), 8020–8025 (2005).
    • 21. Unissa AN, Subbian S, Hanna LE, Selvakumar N. Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis. Infect. Genet. Evol. 45, 474–492 (2016).
    • 22. Dubée V, Triboulet S, Mainardi J-L et al. Inactivation of Mycobacterium tuberculosis l,d-transpeptidase LdtMt1 by carbapenems and cephalosporins. Antimicrob. Agents Chemother. 56(8), 4189–4195 (2012).
    • 23. Kaushik A, Gupta C, Fisher S et al. Combinations of avibactam and carbapenems exhibit enhanced potencies against drug-resistant Mycobacterium abscessus. Future Microbiol. 12(6), 473–480 (2017).
    • 24. Dubée V, Bernut A, Cortes M et al. β-Lactamase inhibition by avibactam in Mycobacterium abscessus. J. Antimicrob. Chemother. 70(4), 1051–1058 (2015).
    • 25. Deshpande D, Srivastava S, Chapagain ML et al. The discovery of ceftazidime/avibactam as an anti-Mycobacterium avium agent. J. Antimicrob. Chemother. 72(Suppl. 2), i36–i42 (2017).
    • 26. Willmott CJ, Critchlow SE, Eperon IC, Maxwell A. The complex of DNA gyrase and quinolone drugs with DNA forms a barrier to transcription by RNA polymerase. J. Mol. Biol. 242(4), 351–363 (1994).
    • 27. Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol. Mol. Biol. Rev. 61(3), 377–392 (1997).
    • 28. Zuckerman JM. Macrolides and ketolides: azithromycin, clarithromycin, telithromycin. Infect. Dis. Clin. North Am. 18(3), 621–649 (2004).
    • 29. Katz L, Ashley GW. Translation and protein synthesis: macrolides. Chem. Rev. 105(2), 499–528 (2005).
    • 30. Suputtamongkol Y. Efficacy and tolerability of linezolid for treatment of nontuberculous mycobacterial diseases. https://clinicaltrials.gov/ct2/show/NCT03220074
    • 31. Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: an overview. Cold Spring Harb. Perspect. Med. 6(6), a027029 (2016).
    • 32. Olivier KN, Griffith DE, Eagle G et al. Randomized trial of liposomal amikacin for inhalation in nontuberculous mycobacterial lung disease. Am. J. Respir. Crit. Care Med. 195(6), 814–823 (2016).
    • 33. Winthrop K. An open-label study of efficacy, safety and tolerability of liposomal amikacin for inhalation (LAI) once daily in addition to standard multi-antibiotic therapy in the treatment of Mycobacterium abscessus lung disease. https://clinicaltrials.gov/ct2/show/NCT03038178
    • 34. Brodersen DE, Clemons WM, Carter AP, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell 103(7), 1143–1154 (2000).
    • 35. Wehrli W. Rifampin: mechanisms of action and resistance. Rev. Infect. Dis. 5(Suppl. 3), S407–S411 (1983).
    • 36. Deoghare S. Bedaquiline: a new drug approved for treatment of multidrug-resistant tuberculosis. Indian J. Pharmacol. 45(5), 536–537 (2013).
    • 37. Lechartier B, Cole ST. Mode of action of clofazimine and combination therapy with benzothiazinones against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 59(8), 4457–4463 (2015).
    • 38. Ruth MM, Sangen JJN, Remmers K et al. A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria. J. Antimicrob. Chemother. 74(4), 935–943 (2019).
    • 39. Erber J, Weidlich S, Tschaikowsky T et al. Successful bedaquiline-containing antimycobacterial treatment in post-traumatic skin and soft-tissue infection by Mycobacterium fortuitum complex: a case report. BMC Infect. Dis. 20(1), 365 (2020).
    • 40. Winthrop K. Phase 2 study of clofazimine for the treatment of pulmonary Mycobacterium avium disease. https://clinicaltrials.gov/ct2/show/NCT02968212
    • 41. McNeil MB, O'Malley T, Dennison D, Shelton CD, Sunde B, Parish T. Multiple mutations in Mycobacterium tuberculosis MmpL3 increase resistance to MmpL3 inhibitors. mSphere 5(5), e00985-20 (2020).
    • 42. Degiacomi G, Benjak A, Madacki J et al. Essentiality of mmpL3 and impact of its silencing on Mycobacterium tuberculosis gene expression. Sci. Rep. 7(1), 43495 (2017).
    • 43. Li W, Yazidi A, Pandya AN et al. MmpL3 as a target for the treatment of drug-resistant nontuberculous mycobacterial infections. Front. Microbiol. 9, 1547 (2018).
    • 44. Xu Z, Meshcheryakov VA, Poce G, Chng S-S. MmpL3 is the flippase for mycolic acids in mycobacteria. Proc. Natl Acad. Sci. USA 114(30), 7993–7998 (2017).
    • 45. Zhang B, Li J, Yang X et al. Crystal structures of membrane transporter MmpL3, an anti-TB drug target. Cell 176(3), 636–648.e13 (2019). • Discusses docking studies of MmpL3 transporter and describes antibiotic interactions with the active site of the enzyme.
    • 46. Ballell L, Bates RH, Young RJ et al. Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis. ChemMedChem 8(2), 313–321 (2013).
    • 47. Dupont C, Viljoen A, Dubar F et al. A new piperidinol derivative targeting mycolic acid transport in Mycobacterium abscessus. Mol. Microbiol. 101(3), 515–529 (2016). • Complete study describing the use of PIPD1 against Mycobacterium abscessus.
    • 48. Onajole OK, Pieroni M, Tipparaju SK et al. Preliminary structure–activity relationships and biological evaluation of novel antitubercular indolecarboxamide derivatives against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains. J. Med. Chem. 56(10), 4093–4103 (2013).
    • 49. Kozikowski AP, Onajole OK, Stec J et al. Targeting mycolic acid transport by indole-2-carboxamides for the treatment of Mycobacterium abscessus infections. J. Med. Chem. 60(13), 5876–5888 (2017).
    • 50. Franz ND, Belardinelli JM, Kaminski MA et al. Design, synthesis and evaluation of indole-2-carboxamides with pan anti-mycobacterial activity. Bioorg. Med. Chem. 25(14), 3746–3755 (2017).
    • 51. Lun S, Guo H, Onajole OK et al. Indoleamides are active against drug-resistant Mycobacterium tuberculosis. Nat. Commun. 4, 2907 (2013).
    • 52. Pandya AN, Prathipati PK, Hegde P et al. Indole-2-carboxamides are active against Mycobacterium abscessus in a mouse model of acute infection. Antimicrob. Agents Chemother. 63(3), e02245-18 (2019). • Most recent in vivo study of indole-2-carboxamides against M. abscessus.
    • 53. Raynaud C, Daher W, Roquet-Banères F et al. Synergistic interactions of indole-2-carboxamides and β-lactam antibiotics against Mycobacterium abscessus. Antimicrob. Agents Chemother. 64(5), e02548-19 (2020).
    • 54. de Ruyck J, Dupont C, Lamy E et al. Structure-based design and synthesis of piperidinol-containing molecules as new Mycobacterium abscessus inhibitors. ChemistryOpen 9(3), 351–365 (2020).
    • 55. Gobis K, Foks H, Serocki M, Augustynowicz-Kopeć E, Napiórkowska A. Synthesis and evaluation of in vitro antimycobacterial activity of novel 1H-benzo[d]imidazole derivatives and analogues. Eur. J. Med. Chem. 89, 13–20 (2015).
    • 56. Raynaud C, Daher W, Johansen MD et al. Active benzimidazole derivatives targeting the MmpL3 transporter in Mycobacterium abscessus. ACS Infect. Dis. 6(2), 324–337 (2020). • Most complete study on the activity of EJMCh-6 against M. abscessus.
    • 57. Korycka-Machała M, Viljoen A, Pawełczyk J et al. 1H-benzo[d]Imidazole derivatives affect MmpL3 in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 63(10), e00441-19 (2019).
    • 58. Muramatsu Y, Muramatsu A, Ohnuki T et al. Studies on novel bacterial translocase I inhibitors, A-500359s. I. Taxonomy, fermentation, isolation, physico-chemical properties and structure elucidation of A-500359 A, C, D and G. J. Antibiot. (Tokyo) 56(3), 243–252 (2003).
    • 59. Bugg TDH, Lloyd AJ, Roper DI. Phospho-MurNAc-pentapeptide translocase (MraY) as a target for antibacterial agents and antibacterial proteins. Infect. Disord. Drug Targets 6(2), 85–106 (2006).
    • 60. Muramatsu Y, Ishii MM, Inukai M. Studies on novel bacterial translocase I inhibitors, A-500359s. II. Biological activities of A-500359 A, C, D and G. J. Antibiot. (Tokyo) 56(3), 253–258 (2003).
    • 61. Hotoda H, Furukawa M, Daigo M et al. Synthesis and antimycobacterial activity of capuramycin analogues. Part 1: substitution of the azepan-2-one moiety of capuramycin. Bioorg. Med. Chem. Lett. 13(17), 2829–2832 (2003).
    • 62. Hotoda H, Daigo M, Furukawa M et al. Synthesis and antimycobacterial activity of capuramycin analogues. Part 2: acylated derivatives of capuramycin-related compounds. Bioorg. Med. Chem. Lett. 13(17), 2833–2836 (2003).
    • 63. Koga T, Fukuoka T, Doi N et al. Activity of capuramycin analogues against Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare in vitro and in vivo. J. Antimicrob. Chemother. 54(4), 755–760 (2004).
    • 64. Reddy VM, Einck L, Nacy CA. In vitro antimycobacterial activities of capuramycin analogues. Antimicrob. Agents Chemother. 52(2), 719–721 (2008).
    • 65. Dubuisson T, Bogatcheva E, Krishnan MY et al. In vitro antimicrobial activities of capuramycin analogues against non-tuberculous mycobacteria. J. Antimicrob. Chemother. 65(12), 2590–2597 (2010).
    • 66. Siricilla S, Mitachi K, Wan B, Franzblau SG, Kurosu M. Discovery of a capuramycin analog that kills nonreplicating Mycobacterium tuberculosis and its synergistic effects with translocase I inhibitors. J. Antibiot. (Tokyo) 68(4), 271–278 (2015).
    • 67. Nikonenko B, Reddy VM, Bogatcheva E, Protopopova M, Einck L, Nacy CA. Therapeutic efficacy of SQ641-NE against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 58(1), 587–589 (2014).
    • 68. Chu DT, Fernandes PB, Claiborne AK, Shen L, Pernet AG. Structure–activity relationships in quinolone antibacterials: design, synthesis and biological activities of novel isothiazoloquinolones. Drugs Exp. Clin. Res. 14(6), 379–383 (1988).
    • 69. Chu DT, Lico IM, Claiborne AK, Plattner JJ, Pernet AG. Structure–activity relationship of quinolone antibacterial agents: the effects of C-2 substitution. Drugs Exp. Clin. Res. 16(5), 215–224 (1990).
    • 70. Kohlbrenner WE, Wideburg N, Weigl D, Saldivar A, Chu DT. Induction of calf thymus topoisomerase II-mediated DNA breakage by the antibacterial isothiazoloquinolones A-65281 and A-65282. Antimicrob. Agents Chemother. 36(1), 81–86 (1992).
    • 71. Bradbury BJ, Hashimoto A, Wang Q, Wiles JA. Method for synthesis of 8-alkoxy-9H-isothiazolo[5,4-b]quinoline-3,4-diones. (2008). https://patents.google.com/patent/WO2008021491A3/no
    • 72. Pucci MJ, Cheng J, Podos SD et al. In vitro and in vivo antibacterial activities of heteroaryl isothiazolones against resistant Gram-positive pathogens. Antimicrob. Agents Chemother. 51(4), 1259–1267 (2007).
    • 73. Wang Q, Lucien E, Hashimoto A et al. Isothiazoloquinolones with enhanced antistaphylococcal activities against multidrug-resistant strains: effects of structural modifications at the 6-, 7-, and 8-positions. J. Med. Chem. 50(2), 199–210 (2007).
    • 74. Bradbury BJ, Wiles JA, Wang Q et al. 8-methoxy-9h-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents. (2014). https://patents.google.com/patent/WO2007014308A1/tr
    • 75. Molina-Torres CA, Ocampo-Candiani J, Rendón A, Pucci MJ, Vera-Cabrera L. In vitro activity of a new isothiazoloquinolone, ACH-702, against Mycobacterium tuberculosis and other mycobacteria. Antimicrob. Agents Chemother. 54(5), 2188–2190 (2010).
    • 76. Pucci MJ, Podos SD, Thanassi JA, Leggio MJ, Bradbury BJ, Deshpande M. In vitro and in vivo profiles of ACH-702, an isothiazoloquinolone, against bacterial pathogens. Antimicrob. Agents Chemother. 55(6), 2860–2871 (2011).
    • 77. US FDA. Determination that ALBAMYCIN (novobiocin sodium) capsule, 250 milligrams, was withdrawn from sale for reasons of safety or effectiveness. Fed. Regist. 76(12), 3143–3144 (2011).
    • 78. Charifson PS, Grillot A-L, Grossman TH et al. Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and structure-activity relationships. J. Med. Chem. 51(17), 5243–5263 (2008).
    • 79. Grillot A-L, Tiran AL, Shannon D et al. Second-generation antibacterial benzimidazole ureas: discovery of a preclinical candidate with reduced metabolic liability. J. Med. Chem. 57(21), 8792–8816 (2014).
    • 80. O'Dowd H, Shannon DE, Chandupatla KR et al. Discovery and characterization of a water-soluble prodrug of a dual inhibitor of bacterial DNA gyrase and topoisomerase IV. ACS Med. Chem. Lett. 6(7), 822–826 (2015).
    • 81. Locher CP, Jones SM, Hanzelka BL et al. A novel inhibitor of gyrase B is a potent drug candidate for treatment of tuberculosis and nontuberculosis mycobacterial infections. Antimicrob. Agents Chemother. 59(3), 1455–1465 (2015).
    • 82. Brown-Elliott BA, Rubio A, Wallace RJ. In vitro susceptibility testing of a novel benzimidazole, SPR719, against nontuberculous mycobacteria. Antimicrob. Agents Chemother. 62(11), e01503-18 (2018). • In vitro study of SPR-719 against a large panel of NTMs.
    • 83. Stokes SS, Vemula R, Pucci MJ. Advancement of GyrB inhibitors for treatment of infections caused by Mycobacterium tuberculosis and non-tuberculous mycobacteria. ACS Infect. Dis. 6(6), 1323–1331 (2020).
    • 84. Spero Therapeutics. A randomized, partially blinded, placebo- and comparator-controlled, multicenter, Phase 2a, dose ranging, proof-of-concept study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of SPR720 as compared with placebo or standard of care for the treatment of patients with Mycobacterium avium complex (MAC) pulmonary disease. https://clinicaltrials.gov/ct2/show/NCT04553406
    • 85. Vinh DC, Rubinstein E. Linezolid: a review of safety and tolerability. J. Infect. 59(Suppl. 1), S59–S74 (2009).
    • 86. Winthrop KL, Ku JH, Marras TK et al. The tolerability of linezolid in the treatment of nontuberculous mycobacterial disease. Eur. Respir. J. 45(4), 1177–1179 (2015).
    • 87. Fala L. Sivextro (tedizolid phosphate) approved for the treatment of adults with acute bacterial skin and skin-structure infections. Am. Health Drug Benefits. 8(Spec Feature), 111–115 (2015).
    • 88. Tang YW, Cheng B, Yeoh SF, Lin RTP, Teo JWP. Tedizolid activity against clinical Mycobacterium abscessus complex isolates – an in vitro characterization study. Front. Microbiol. 9, 2095 (2018).
    • 89. Brown-Elliott BA, Wallace RJ. In vitro susceptibility testing of tedizolid against nontuberculous mycobacteria. J. Clin. Microbiol. 55(6), 1747–1754 (2017).
    • 90. Kanafani ZA, Corey GR. Tedizolid (TR-701): a new oxazolidinone with enhanced potency. Expert Opin. Investig. Drugs 21(4), 515–522 (2012).
    • 91. Flanagan SD, Bien PA, Muñoz KA, Minassian SL, Prokocimer PG. Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food, and comparison of two solid forms of the prodrug. Pharmacotherapy 34(3), 240–250 (2014).
    • 92. LegoChem Biosciences, Inc. A Phase IIb, open label, randomized controlled dose ranging multi-center trial to evaluate the safety, tolerability, pharmacokinetics and exposure–response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis. https://clinicaltrials.gov/ct2/show/NCT04550832
    • 93. Jeong J-W, Jung S-J, Lee H-H et al. In vitro and in vivo activities of LCB01-0371, a new oxazolidinone. Antimicrob. Agents Chemother. 54(12), 5359–5362 (2010).
    • 94. Kim TS, Choe JH, Kim YJ et al. Activity of LCB01-0371, a novel oxazolidinone, against Mycobacterium abscessus. Antimicrob. Agents Chemother. 61(9), e02752–16 (2017). • In vitro and in vivo study of delpazolid against M. abscessus.
    • 95. Shoen C, Benaroch D, Sklaney M, Cynamon M. In vitro activities of omadacycline against rapidly growing mycobacteria. Antimicrob. Agents Chemother. 63(5), e02522-18 (2019).
    • 96. Xiao X-Y, Hunt DK, Zhou J et al. Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent. J. Med. Chem. 55(2), 597–605 (2012).
    • 97. Pioletti M, Schlünzen F, Harms J et al. Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3. EMBO J. 20(8), 1829–1839 (2001).
    • 98. Honeyman L, Ismail M, Nelson ML et al. Structure–activity relationship of the aminomethylcyclines and the discovery of omadacycline. Antimicrob. Agents Chemother. 59(11), 7044–7053 (2015).
    • 99. Clark RB, Hunt DK, He M et al. Fluorocyclines. 2. Optimization of the C-9 side-chain for antibacterial activity and oral efficacy. J. Med. Chem. 55(2), 606–622 (2012).
    • 100. Cynamon M, Jureller J, Desai B, Ramachandran K, Sklaney M, Grossman TH. In vitro activity of TP-271 against Mycobacterium abscessus, Mycobacterium fortuitum, and Nocardia species. Antimicrob. Agents Chemother. 56(7), 3986–3988 (2012).
    • 101. Kaushik A, Ammerman NC, Martins O, Parrish NM, Nuermberger EL. In vitro activity of new tetracycline analogs omadacycline and eravacycline against drug-resistant clinical isolates of Mycobacterium abscessus. Antimicrob. Agents Chemother. 63(6), e00470-19 (2019).
    • 102. Seibert G, Toti L, Wink J. Treating mycobacterial infections with cyclipostins (2008). https://patents.google.com/patent/WO2008025449A1/fr
    • 103. Nguyen PC, Madani A, Santucci P et al. Cyclophostin and cyclipostins analogues, new promising molecules to treat mycobacterial-related diseases. Int. J. Antimicrob. Agents 51(4), 651–654 (2018).
    • 104. Point V, Malla RK, Diomande S et al. Synthesis and kinetic evaluation of cyclophostin and cyclipostins phosphonate analogs as selective and potent inhibitors of microbial lipases. J. Med. Chem. 55(22), 10204–10219 (2012).
    • 105. Nguyen PC, Delorme V, Bénarouche A et al. Cyclipostins and cyclophostin analogs as promising compounds in the fight against tuberculosis. Sci. Rep. 7(1), 11751 (2017).
    • 106. Madani A, Ridenour JN, Martin BP et al. Cyclipostins and cyclophostin analogues as multitarget inhibitors that impair growth of Mycobacterium abscessus. ACS Infect. Dis. 5(9), 1597–1608 (2019).
    • 107. Viljoen A, Richard M, Nguyen PC et al. Cyclipostins and cyclophostin analogs inhibit the antigen 85C from Mycobacterium tuberculosis both in vitro and in vivo. J. Biol. Chem. 293(8), 2755–2769 (2018).
    • 108. Waisser K, Bures O, Holý P et al. Relationship between the structure and antimycobacterial activity of substituted salicylanilides. Arch. Pharm. (Weinheim) 336(1), 53–71 (2003).
    • 109. Krátký M, Vinšová J, Novotná E et al. Salicylanilide derivatives block Mycobacterium tuberculosis through inhibition of isocitrate lyase and methionine aminopeptidase. Tuberculosis 92(5), 434–439 (2012).
    • 110. Wu W-S, Cheng W-C, Cheng T-JR, Wong C-H. Affinity-based screen for inhibitors of bacterial transglycosylase. J. Am. Chem. Soc. 140(8), 2752–2755 (2018).
    • 111. Triola G, Wetzel S, Ellinger B et al. ATP competitive inhibitors of D-alanine-D-alanine ligase based on protein kinase inhibitor scaffolds. Bioorg. Med. Chem. 17(3), 1079–1087 (2009).
    • 112. Lee I-Y, Gruber TD, Samuels A et al. Structure–activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling. Bioorg. Med. Chem. 21(1), 114–126 (2013).
    • 113. Krátký M, Vinšová J, Novotná E, Stolaříková J. Salicylanilide pyrazinoates inhibit in vitro multidrug-resistant Mycobacterium tuberculosis strains, atypical mycobacteria and isocitrate lyase. Eur. J. Pharm. Sci. 53, 1–9 (2014).
    • 114. Krátký M, Bősze S, Baranyai Z et al. Synthesis and in vitro biological evaluation of 2-(phenylcarbamoyl)phenyl 4-substituted benzoates. Bioorg. Med. Chem. 23(4), 868–875 (2015).
    • 115. Baranyai Z, Krátký M, Vinšová J et al. Combating highly resistant emerging pathogen Mycobacterium abscessus and Mycobacterium tuberculosis with novel salicylanilide esters and carbamates. Eur. J. Med. Chem. 101, 692–704 (2015).
    • 116. O'Malley T, Alling T, Early JV et al. Imidazopyridine compounds inhibit mycobacterial growth by depleting ATP levels. Antimicrob. Agents Chemother. 62(6), e02439-17 (2018).
    • 117. Moraski GC, Markley LD, Hipskind PA et al. Advent of imidazo[1,2-a]pyridine-3-carboxamides with potent multi- and extended drug resistant antituberculosis activity. ACS Med. Chem. Lett. 2(6), 466–470 (2011).
    • 118. Moraski GC, Markley LD, Cramer J et al. Advancement of imidazo[1,2-a]pyridines with improved pharmacokinetics and nM activity vs. Mycobacterium tuberculosis. ACS Med. Chem. Lett. 4(7), 675–679 (2013).
    • 119. Moraski GC, Cheng Y, Cho S et al. Imidazo[1,2-a]pyridine-3-carboxamides are active antimicrobial agents against Mycobacterium avium infection in vivo. Antimicrob. Agents Chemother. 60(8), 5018–5022 (2016). • In vivo study of the use of imidazo[1,2-a]pyridines (IAPs) against Mycobacterium avium.