1887

Abstract

There is a need for new combination regimens for tuberculosis. Identifying synergistic drug combinations can avoid toxic side effects and reduce treatment times. Using a fluorescent rifampicin conjugate, we demonstrated that synergy between cell wall inhibitors and rifampicin was associated with increased accumulation of rifampicin. Increased accumulation was also associated with increased cellular permeability.

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2019-03-20
2019-09-22
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References

  1. WHO, World Health Organisation Global Tuberculosis report 2017 2017
    [Google Scholar]
  2. Jia J, Zhu F, Ma X, Cao Z, Cao ZW et al. Mechanisms of drug combinations: interaction and network perspectives. Nat Rev Drug Discov 2009;8:111–128 [CrossRef]
    [Google Scholar]
  3. Li W, Obregón-Henao A, Wallach JB, North EJ, Lee RE et al. Therapeutic potential of the Mycobacterium tuberculosis mycolic acid transporter, MmpL3. Antimicrob Agents Chemother 2016;60:5198–5207 [CrossRef]
    [Google Scholar]
  4. Li W, Sanchez-Hidalgo A, Jones V, de Moura VCN, North EJ et al. Synergistic interactions of MmpL3 inhibitors with antitubercular compounds in vitro. Antimicrob Agents Chemother 2017;61:e02399–16 [CrossRef]
    [Google Scholar]
  5. Stec J, Onajole OK, Lun S, Guo H, Merenbloom B et al. Indole-2-carboxamide-based MmpL3 inhibitors show exceptional antitubercular activity in an animal model of tuberculosis infection. J Med Chem 2016;59:6232–6247 [CrossRef]
    [Google Scholar]
  6. Grzegorzewicz AE, Pham H, Gundi VAKB, Scherman MS, North EJ et al. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol 2012;8:334–341 [CrossRef]
    [Google Scholar]
  7. Chen P, Gearhart J, Protopopova M, Einck L, Nacy CA et al. Synergistic interactions of SQ109, a new ethylene diamine, with front-line antitubercular drugs in vitro. J Antimicrob Chemother 2006;58:332–337 [CrossRef]
    [Google Scholar]
  8. Piddock LJV, Williams KJ, Ricci V. Accumulation of rifampicin by Mycobacterium aurum, Mycobacterium smegmatis and Mycobacterium tuberculosis. J Antimicrob Chemother 2000;45:159–165 [CrossRef]
    [Google Scholar]
  9. Aggarwal A, Parai MK, Shetty N, Wallis D, Woolhiser L et al. Development of a novel lead that targets M. tuberculosis polyketide synthase 13. Cell 2017;170:249–259 [CrossRef]
    [Google Scholar]
  10. Ollinger J, Bailey MA, Moraski GC, Casey A, Florio S et al. A dual read-out assay to evaluate the potency of compounds active against Mycobacterium tuberculosis. PLoS One 2013;8:e60531 [CrossRef]
    [Google Scholar]
  11. Lambert RJ, Pearson J. Susceptibility testing: accurate and reproducible minimum inhibitory concentration (MIC) and non-inhibitory concentration (NiC) values. J Appl Microbiol 2000;88:784–790 [CrossRef]
    [Google Scholar]
  12. Mikusová K, Slayden RA, Besra GS, Brennan PJ. Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. Antimicrob Agents Chemother 1995;39:2484–2489 [CrossRef]
    [Google Scholar]
  13. Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 1994;263:227–230 [CrossRef]
    [Google Scholar]
  14. Wilson R, Kumar P, Parashar V, Vilchèze C, Veyron-Churlet R et al. Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis. Nat Chem Biol 2013;9:499–506 [CrossRef]
    [Google Scholar]
  15. Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 2000;405:962–966 [CrossRef]
    [Google Scholar]
  16. Andries K, Verhasselt P, Guillemont J, Göhlmann HWH, Neefs JM et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005;307:223–227 [CrossRef]
    [Google Scholar]
  17. Rodrigues L, Wagner D, Viveiros M, Sampaio D, Couto I et al. Thioridazine and chlorpromazine inhibition of ethidium bromide efflux in Mycobacterium avium and Mycobacterium smegmatis. J Antimicrob Chemother 2008;61:1076–1082 [CrossRef]
    [Google Scholar]
  18. Ramón-García S, González Del Río R, Villarejo AS, Sweet GD, Cunningham F et al. Repurposing clinically approved cephalosporins for tuberculosis therapy. Sci Rep 2016;6:34293 [CrossRef]
    [Google Scholar]
  19. Manjunatha U, Boshoff HIM, Barry CE. The mechanism of action of PA-824. Commun Integr Biol 2009;2:215–218 [CrossRef]
    [Google Scholar]
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