1887

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Volume 67, Issue 3

Antimicrobial activity against under lipid-rich dormancy conditions Free

Abstract

Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of to two antibiotic combinations – rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) – in a lipid-rich dormancy model. Although their effectiveness in cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): dormancy model , dormant mycobacteria , drug susceptibility testing , drug-tolerant mycobacteria , lipids as carbon source and treatment failures and relapses
© 2018 The Authors
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2018-03-01
2024-04-25
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References

  1. Bryant JM, Harris SR, Parkhill J, Dawson R, Diacon AH et al. Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study. Lancet Respir Med 2013; 1:786–792 [View Article][PubMed]
     [Google Scholar]
  2. Peddireddy V, Doddam SN, Ahmed N. Mycobacterial dormancy systems and host responses in tuberculosis. Front Immunol 2017; 8:1–19 [View Article]
     [Google Scholar]
  3. Aguilar-Ayala DA, Palomino JC, Vandamme P, Martin A, Gonzalez-Y-Merchand JA. “Genetic regulation of Mycobacterium tuberculosis in a lipid-rich environment”. Infect Genet Evol 2017; 55:392–402 [View Article][PubMed]
     [Google Scholar]
  4. Barisch C, Soldati T. Breaking fat! How mycobacteria and other intracellular pathogens manipulate host lipid droplets. Biochimie 2017; 141:54–61 [View Article][PubMed]
     [Google Scholar]
  5. Soto-Ramirez MD, Aguilar-Ayala DA, Garcia-Morales L, Rodriguez-Peredo SM, Badillo-Lopez C et al. Cholesterol plays a larger role during Mycobacterium tuberculosis in vitro dormancy and reactivation than previously suspected. Tuberculosis 2017; 103:1–9 [View Article][PubMed]
     [Google Scholar]
  6. 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; 64:2062–2069[PubMed]
     [Google Scholar]
  7. Filippini P, Iona E, Piccaro G, Peyron P, Neyrolles O et al. Activity of drug combinations against dormant Mycobacterium tuberculosis. Antimicrob Agents Chemother 2010; 54:2712–2715 [View Article][PubMed]
     [Google Scholar]
  8. Piccaro G, Giannoni F, Filippini P, Mustazzolu A, Fattorini L. Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions. Antimicrob Agents Chemother 2013; 57:1428–1433 [View Article][PubMed]
     [Google Scholar]
  9. Blodgett R.Food and Drug Administration Bacteriological analytical manual. Appendix 2: Most Probable Number from Serial Dilutions Available from www.fda.gov/food/foodscienceresearch/laboratorymethods/ucm109656.htm
  10. Piccaro G, Filippini P, Giannoni F, Scipione L, Tortorella S et al. Activity of drugs against dormant Mycobacterium tuberculosis. J Chemother 2011; 23:175–178 [View Article][PubMed]
     [Google Scholar]
  11. Carroll MW, Jeon D, Mountz JM, Lee JD, Jeong YJ et al. Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis. Antimicrob Agents Chemother 2013; 57:3903–3909 [View Article][PubMed]
     [Google Scholar]
  12. Amato SM, Orman MA, Brynildsen MP. Metabolic control of persister formation in Escherichia coli. Mol Cell 2013; 50:475–487 [View Article][PubMed]
     [Google Scholar]
  13. Ersoy SC, Heithoff DM, Barnes L, Tripp GK, House JK et al. Correcting a fundamental flaw in the paradigm for antimicrobial susceptibility testing. EBioMedicine 2017; 20:173–181 [View Article][PubMed]
     [Google Scholar]
  14. Orman MA, Brynildsen MP. Dormancy is not necessary or sufficient for bacterial persistence. Antimicrob Agents Chemother 2013; 57:3230–3239 [View Article][PubMed]
     [Google Scholar]
  15. Allison KR, Brynildsen MP, Collins JJ. Heterogeneous bacterial persisters and engineering approaches to eliminate them. Curr Opin Microbiol 2011; 14:593–598 [View Article][PubMed]
     [Google Scholar]
  16. Barr DA, Kamdolozi M, Nishihara Y, Ndhlovu V, Khonga M et al. Serial image analysis of Mycobacterium tuberculosis colony growth reveals a persistent subpopulation in sputum during treatment of pulmonary TB. Tuberculosis 2016; 98:110–115 [View Article][PubMed]
     [Google Scholar]
  17. Hong MS, Kim Y, Cho EJ, Lee JS, Kwak HK et al. Comparison of the characteristics of Mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients. Eur J Clin Microbiol Infect Dis 2017; 36:2063–2072 [View Article][PubMed]
     [Google Scholar]
  18. Dartois V, Saito K, Warrier T, Nathan C. New evidence for the complexity of the population structure of Mycobacterium tuberculosis increases the diagnostic and biologic challenges. Am J Respir Crit Care Med 2016; 194:1448–1451 [View Article][PubMed]
     [Google Scholar]
  19. Levin-Reisman I, Ronin I, Gefen O, Braniss I, Shoresh N et al. Antibiotic tolerance facilitates the evolution of resistance. Science 2017; 355:826–830 [View Article][PubMed]
     [Google Scholar]
  20. Soni I, de Groote MA, Dasgupta A, Chopra S. Challenges facing the drug discovery pipeline for non-tuberculous mycobacteria. J Med Microbiol 2016; 65:1–8 [View Article][PubMed]
     [Google Scholar]
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Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions
J. Med. Microbiol. 67, 282 (2018); https://doi.org/10.1099/jmm.0.000681
/content/journal/jmm/10.1099/jmm.0.000681
/content/journal/jmm/10.1099/jmm.0.000681
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