Effects of deferoxamine on intrinsic colistin resistance of .

Mehmet Erinmez, Yasemin Zer
Author Information
  1. Mehmet Erinmez: Department of Medical Microbiology, Gaziantep University School of Medicine, 27310 Gaziantep, Turkey.
  2. Yasemin Zer: Department of Medical Microbiology, Gaziantep University School of Medicine, 27310 Gaziantep, Turkey.

Abstract

is a common pathogen, which is responsible for urinary tract infections. Iron is a critical element necessary for both humans and pathogens to maintain their biological functions, and iron limitation via chelator agents may be useful in the treatment of infections. The present study aimed to investigate the synergistic interactions between the iron chelator agent deferoxamine (DFO) and the antibacterial drug colistin. The minimum inhibitory concentration (MIC) values of DFO and colistin for isolates were determined by broth microdilution. The checkerboard technique was used to examine the potential synergy between DFO and colistin. Furthermore, time-kill assays were used for the confirmation of synergy detected by the checkerboard assay, as well as for determining bacteriostatic and bactericidal interactions throughout a 24-h period. As expected, all isolates were resistant to colistin. DFO did not inhibit growth when used alone, even at very high doses (10 µg ml). Notably, when in combination with DFO, the MIC values of colistin were markedly reduced, and the checkerboard assay results showed synergy between colistin and DFO for all isolates. In addition, in time-kill assays, colistin + DFO exhibited synergistic activity against all strains at most time intervals and concentrations tested. Colistin + DFO showed bactericidal activity at colistin concentrations of 1xMIC and 2xMIC, although a degree of re-growth was observed in one of the strains at 12-24 h. These findings indicated that DFO has the potential for use as an adjunct to colistin through iron sequestration, thus providing synergistic activity to an antibiotic that would not normally be considered a treatment option against experiments in the future may provide useful information on the efficacy of DFO/colistin since these models effectively reflect physiological parameters.

Keywords

References

  1. Biochim Biophys Acta. 2015 Jul;1852(7):1347-59 [PMID: 25843914]
  2. West Afr J Med. 2011 Jul-Aug;30(4):268-72 [PMID: 22669831]
  3. Annu Rev Pharmacol Toxicol. 2013;53:17-36 [PMID: 23020294]
  4. Antimicrob Agents Chemother. 2012 Oct;56(10):5419-21 [PMID: 22850524]
  5. J Pharm Pharmacol. 2011 Jul;63(7):893-903 [PMID: 21635254]
  6. Urol Int. 2021;105(5-6):354-361 [PMID: 33691318]
  7. Annu Rev Genet. 2016 Nov 23;50:67-91 [PMID: 27617971]
  8. Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L799-805 [PMID: 11053013]
  9. FEMS Microbiol Lett. 2010 Jun;307(1):19-24 [PMID: 20402789]
  10. Antibiotics (Basel). 2020 Feb 03;9(2): [PMID: 32028684]
  11. Curr Drug Deliv. 2010 Jul;7(3):194-207 [PMID: 20507267]
  12. Microb Ecol. 2016 Nov;72(4):741-758 [PMID: 26748500]
  13. Metallomics. 2015 Jun;7(6):935-42 [PMID: 25677827]
  14. Lancet. 2013 Jul 6;382(9886):29-40 [PMID: 23602230]
  15. Pediatrics. 2009 Apr;123(4):1208-16 [PMID: 19336381]
  16. Front Med (Lausanne). 2021 Aug 12;8:677720 [PMID: 34476235]
  17. Front Cell Infect Microbiol. 2020 Aug 14;10:414 [PMID: 32923408]
  18. Hemoglobin. 2010 Jun;34(3):227-39 [PMID: 20524813]
  19. Infect Drug Resist. 2018 Jan 09;11:61-75 [PMID: 29386910]
  20. Med Res Rev. 2002 Jan;22(1):26-64 [PMID: 11746175]
  21. Int J Mol Sci. 2021 Mar 12;22(6): [PMID: 33809032]
  22. Appl Environ Microbiol. 2010 Jun;76(12):3836-41 [PMID: 20418434]
  23. Antimicrob Agents Chemother. 2009 Aug;53(8):3430-6 [PMID: 19433570]
  24. Diagn Microbiol Infect Dis. 2018 Dec;92(4):338-345 [PMID: 30097297]
  25. Curr Urol Rep. 2001 Aug;2(4):330-3 [PMID: 12084261]
  26. Front Cell Infect Microbiol. 2018 Oct 16;8:344 [PMID: 30460202]
  27. J Infect Dis. 2004 Oct 1;190(7):1245-53 [PMID: 15346334]
  28. Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13462-13467 [PMID: 27821741]
  29. EcoSal Plus. 2018 Feb;8(1): [PMID: 29424333]
  30. Emerg Microbes Infect. 2020 Dec;9(1):868-885 [PMID: 32284036]
  31. Methods Mol Biol. 2019;2021:1-4 [PMID: 31309490]
  32. Curr Res Microb Sci. 2021 Aug 17;2:100060 [PMID: 34841350]
  33. Am J Respir Cell Mol Biol. 2009 Sep;41(3):305-13 [PMID: 19168700]
  34. Curr Med Chem. 2018;25(1):85-96 [PMID: 28730969]
  35. Sci Rep. 2018 May 8;8(1):7237 [PMID: 29740150]
  36. Int J Antimicrob Agents. 2019 May;53(5):612-619 [PMID: 30682497]
  37. PLoS One. 2013;8(1):e53756 [PMID: 23326499]
  38. Am J Physiol Renal Physiol. 2019 May 1;316(5):F814-F822 [PMID: 30724105]
  39. Nutr Metab Insights. 2014 May 26;7:47-50 [PMID: 24932105]
  40. Appl Environ Microbiol. 2006 Mar;72(3):2064-9 [PMID: 16517655]
  41. Microbiol Spectr. 2021 Dec 22;9(3):e0123121 [PMID: 34730415]
  42. FEMS Microbiol Rev. 2015 Jul;39(4):592-630 [PMID: 25862688]
  43. Autophagy. 2016 May 3;12(5):850-63 [PMID: 27002654]
  44. PLoS One. 2012;7(5):e37350 [PMID: 22606361]
  45. FEMS Microbiol Rev. 2003 Jun;27(2-3):215-37 [PMID: 12829269]
  46. Acta Biomater. 2021 May;126:384-393 [PMID: 33705987]
  47. Clin Perinatol. 2015 Mar;42(1):17-28, vii [PMID: 25677994]
  48. PLoS One. 2015 Jun 11;10(6):e0126479 [PMID: 26067824]
  49. Urol Clin North Am. 2015 Nov;42(4):561-8 [PMID: 26475952]
  50. Lancet Infect Dis. 2019 Jan;19(1):56-66 [PMID: 30409683]
  51. Molecules. 2021 Jan 02;26(1): [PMID: 33401708]
  52. Curr Drug Targets. 2016;17(9):1029-50 [PMID: 26424398]
  53. Elife. 2021 Apr 06;10: [PMID: 33821795]
  54. Immunology. 2020 Nov;161(3):186-199 [PMID: 32639029]
  55. Shock. 2016 Dec;46(6):597-608 [PMID: 27454373]
  56. Nat Rev Microbiol. 2020 Mar;18(3):152-163 [PMID: 31748738]
  57. Gut Microbes. 2021 Jan-Dec;13(1):1-19 [PMID: 33541211]
  58. Antimicrob Agents Chemother. 2017 Dec 21;62(1): [PMID: 29061741]