Azathioprine, Mercaptopurine, and 5-Aminosalicylic Acid Affect the Growth of IBD-Associated Species and Other Enteric Microbes.

Fang Liu, Rena Ma, Stephen M Riordan, Michael C Grimm, Lu Liu, Yiming Wang, Li Zhang
Author Information
  1. Fang Liu: School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia.
  2. Rena Ma: School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia.
  3. Stephen M Riordan: Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South WalesSydney, NSW, Australia.
  4. Michael C Grimm: St George and Sutherland Clinical School, University of New South WalesSydney, NSW, Australia.
  5. Lu Liu: School of Medical Sciences, University of New South WalesSydney, NSW, Australia.
  6. Yiming Wang: School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia.
  7. Li Zhang: School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia.

Abstract

is a bacterium that is associated with inflammatory bowel disease (IBD). Immunosuppressive drugs including azathioprine (AZA) and mercaptopurine (MP), and anti-inflammatory drug such as 5-aminosalicylic acid (5-ASA) are commonly used to treat patients with IBD. This study aimed to examine the effects of AZA, MP, and 5-ASA on the growth of IBD-associated bacterial species and to identify bacterial enzymes involved in immunosuppressive drug metabolism. A total of 15 bacterial strains of five species including 11 strains, , and were examined. The impact of AZA, MP, and 5-ASA on the growth of these bacterial species was examined quantitatively using a plate counting method. The presence of enzymes involved in AZA and MP metabolism in these bacterial species was identified using bioinformatics tools. AZA and MP significantly inhibited the growth of all 11 strains. strains were more sensitive to AZA than MP. 5-ASA showed inhibitory effects to some strains, while it promoted the growth of other strains. AZA and MP also significantly inhibited the growth of and . The growth of was significantly inhibited by 200 μg/ml of AZA as well as 100 and 200 μg/ml of 5-ASA. Bacterial enzymes related to AZA and MP metabolism were found, which varied in different bacterial species. In conclusion, AZA and MP have inhibitory effects to IBD-associated and other enteric microbes, suggesting an additional therapeutic mechanism of these drugs in the treatment of IBD. The strain dependent differential impact of 5-ASA on the growth of may also have clinical implication given that in some cases 5-ASA medications were found to cause exacerbations of colitis.

Keywords

References

  1. Med Res Rev. 2014 Mar;34(2):340-437 [PMID: 23740514]
  2. J Clin Microbiol. 2006 Mar;44(3):1204-5 [PMID: 16517933]
  3. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67 [PMID: 18506437]
  4. PLoS One. 2013 Sep 23;8(9):e75525 [PMID: 24086553]
  5. Reg Immunol. 1990 Jan-Feb;3(1):56-61 [PMID: 2223557]
  6. Antimicrob Agents Chemother. 2008 Feb;52(2):418-26 [PMID: 18070971]
  7. PLoS One. 2013;8(2):e56888 [PMID: 23437263]
  8. Gut Pathog. 2016 May 18;8:18 [PMID: 27195022]
  9. Gut Pathog. 2016 Sep 15;8:43 [PMID: 27651834]
  10. J Clin Microbiol. 1990 Mar;28(3):435-7 [PMID: 2108992]
  11. Gut Pathog. 2016 Jun 01;8:27 [PMID: 27252786]
  12. Microbiology. 2015 Aug;161(8):1600-12 [PMID: 26002953]
  13. PLoS One. 2011;6(8):e23858 [PMID: 21887334]
  14. World J Gastroenterol. 2015 Aug 21;21(31):9239-44 [PMID: 26309350]
  15. Hepatogastroenterology. 1981 Aug;28(4):192-4 [PMID: 7274981]
  16. Int J Microbiol. 2014;2014:476047 [PMID: 25214843]
  17. Dig Dis Sci. 2000 Aug;45(8):1601-7 [PMID: 11007112]
  18. Aliment Pharmacol Ther. 2000 Aug;14(8):1009-14 [PMID: 10930894]
  19. Aliment Pharmacol Ther. 2006 Sep 1;24(5):715-29 [PMID: 16918876]
  20. J Clin Pathol. 1973 Jun;26(6):393-5 [PMID: 4718964]
  21. Gut. 1996 Jul;39(1):63-8 [PMID: 8881811]
  22. Ann Intern Med. 1995 Jul 15;123(2):132-42 [PMID: 7778826]
  23. J Appl Microbiol. 1998 Jul;85(1):25-36 [PMID: 9721653]
  24. Sci Rep. 2016 Dec 02;6:38442 [PMID: 27910936]
  25. Gut. 1992 Jul;33(7):890-6 [PMID: 1644328]
  26. Gastroenterology. 2003 May;124(5):1265-76 [PMID: 12730867]
  27. Appl Environ Microbiol. 1978 May;35(5):988-91 [PMID: 655716]
  28. PLoS One. 2007 Jan 24;2(1):e161 [PMID: 17252054]
  29. J Clin Microbiol. 2010 Aug;48(8):2965-7 [PMID: 20519479]
  30. Infect Immun. 1981 Apr;32(1):225-31 [PMID: 7216487]
  31. Mol Pharmacol. 2006 Aug;70(2):747-54 [PMID: 16717136]
  32. Clin Microbiol Rev. 2007 Oct;20(4):593-621 [PMID: 17934076]
  33. Br J Dermatol. 2011 Oct;165(4):711-34 [PMID: 21950502]
  34. Clin Sci (Lond). 1990 Feb;78(2):119-25 [PMID: 2155736]
  35. Clin Microbiol Infect. 2013 May;19(5):445-50 [PMID: 22512739]
  36. J Clin Microbiol. 2000 Dec;38(12):4373-81 [PMID: 11101567]
  37. PLoS One. 2011;6(6):e21490 [PMID: 21738679]
  38. Nucleic Acids Res. 2007 Jan;35(Database issue):D61-5 [PMID: 17130148]
  39. PLoS One. 2011;6(9):e25417 [PMID: 21966525]
  40. N Engl J Med. 1982 Feb 18;306(7):409-12 [PMID: 6120459]
  41. J Exp Med. 2005 Apr 18;201(8):1205-15 [PMID: 15824083]
  42. J Med Microbiol. 2015 Apr;64(Pt 4):438-45 [PMID: 25657299]
  43. Aliment Pharmacol Ther. 2006 Oct;24 Suppl 3:37-40 [PMID: 16961743]
  44. Bacteriol Rev. 1972 Dec;36(4):525-57 [PMID: 4568763]
  45. Scand J Infect Dis. 1995;27(2):187-8 [PMID: 7660089]
  46. Neth J Med. 1997 Feb;50(2):S12-4 [PMID: 9050327]
  47. Emerg Infect Dis. 2000 Mar-Apr;6(2):171-4 [PMID: 10756151]
  48. Int J Food Sci Nutr. 2016;67(2):83-91 [PMID: 26754553]
  49. Cochrane Database Syst Rev. 2015 Oct 30;(10):CD000067 [PMID: 26517527]
  50. Cochrane Database Syst Rev. 2016 May 18;(5):CD000478 [PMID: 27192092]
  51. Dig Dis Sci. 2009 Jun;54(6):1157-70 [PMID: 18770034]
  52. Eur J Gastroenterol Hepatol. 2005 Oct;17(10):1019-24 [PMID: 16148545]
  53. BMC Microbiol. 2011 Mar 15;11:53 [PMID: 21406111]
  54. J Clin Microbiol. 2009 Feb;47(2):453-5 [PMID: 19052183]
  55. Cochrane Database Syst Rev. 2016 Oct 26;10 :CD000545 [PMID: 27783843]
  56. Cochrane Database Syst Rev. 2016 Apr 21;4:CD000543 [PMID: 27101467]
  57. Ann N Y Acad Sci. 1993 Jun 23;685:400-7 [PMID: 8363248]
  58. World J Gastroenterol. 2014 Feb 7;20(5):1259-67 [PMID: 24574800]
  59. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D115-9 [PMID: 14681372]
  60. Aliment Pharmacol Ther. 2001 Nov;15(11):1699-708 [PMID: 11683683]
  61. PLoS One. 2012;7(5):e38217 [PMID: 22666490]
  62. Am J Pathol. 2002 Jun;160(6):2253-7 [PMID: 12057927]

Word Cloud

Created with Highcharts 10.0.0AZAMP5-ASAgrowthbacterialstrainsspeciesdrugIBDeffectsenzymesmetabolismsignificantlyinhibitedinflammatoryboweldiseasedrugsincludingazathioprinemercaptopurineanti-inflammatory5-aminosalicylicacidIBD-associatedinvolvedimmunosuppressive11examinedimpactusinginhibitoryalso200μg/mlfoundentericbacteriumassociatedImmunosuppressivecommonlyusedtreatpatientsstudyaimedexamineidentifytotal15fivequantitativelyplatecountingmethodpresenceidentifiedbioinformaticstoolssensitiveshowedpromotedwell100BacterialrelatedvarieddifferentconclusionmicrobessuggestingadditionaltherapeuticmechanismtreatmentstraindependentdifferentialmayclinicalimplicationgivencasesmedicationscauseexacerbationscolitisAzathioprineMercaptopurine5-AminosalicylicAcidAffectGrowthIBD-AssociatedSpeciesEntericMicrobesCampylobacterconcisusbacteria

Similar Articles

Cited By