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Lau SK, Lam CW, Curreem SO, et al. Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway. Cell Biosci. 2015;5:26doi: 10.1186/s13578-015-0018-x.
Lau, S. K., Lam, C. W., Curreem, S. O., Lee, K. C., Chow, W. N., Lau, C. C., Sridhar, S., Wong, S. C., Martelli, P., Hui, S. W., Yuen, K. Y., & Woo, P. C. (2015). Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway. Cell & bioscience, 526. https://doi.org/10.1186/s13578-015-0018-x
Lau, Susanna K P, et al. "Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway." Cell & bioscience vol. 5 (2015): 26. doi: https://doi.org/10.1186/s13578-015-0018-x
Lau SK, Lam CW, Curreem SO, Lee KC, Chow WN, Lau CC, Sridhar S, Wong SC, Martelli P, Hui SW, Yuen KY, Woo PC. Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway. Cell Biosci. 2015 Jun 02;5:26. doi: 10.1186/s13578-015-0018-x. eCollection 2015. PMID: 26097677; PMCID: PMC4475313.
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Cell Biosci. 2015 Jun 02;5:26. doi: 10.1186/s13578-015-0018-x. eCollection 2015.

Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway.

Cell & bioscience

Susanna K P Lau, Ching-Wan Lam, Shirly O T Curreem, Kim-Chung Lee, Wang-Ngai Chow, Candy C Y Lau, Siddharth Sridhar, Sally C Y Wong, Paolo Martelli, Suk-Wai Hui, Kwok-Yung Yuen, Patrick C Y Woo

Affiliations

  1. State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Room 423, University Pathology Building, Queen Mary Hospital, Pok Fu Lam, Hong Kong ; Research Centre of Infection and Immunology, The University of Hong Kong, Pok Fu Lam, Hong Kong ; Carol Yu Centre for Infection, The University of Hong Kong, Pok Fu Lam, Hong Kong ; Department of Microbiology, The University of Hong Kong, Pok Fu Lam, Hong Kong.
  2. Department of Pathology, The University of Hong Kong, Pok Fu Lam, Hong Kong.
  3. Department of Microbiology, The University of Hong Kong, Pok Fu Lam, Hong Kong.
  4. Ocean Park Corporation, Aqua City, Hong Kong.

PMID: 26097677 PMCID: PMC4475313 DOI: 10.1186/s13578-015-0018-x

Abstract

BACKGROUND: Burkholderia pseudomallei is an emerging pathogen that causes melioidosis, a serious and potentially fatal disease which requires prolonged antibiotics to prevent relapse. However, diagnosis of melioidosis can be difficult, especially in culture-negative cases. While metabolomics represents an uprising tool for studying infectious diseases, there were no reports on its applications to B. pseudomallei. To search for potential specific biomarkers, we compared the metabolomics profiles of culture supernatants of B. pseudomallei (15 strains), B. thailandensis (3 strains), B. cepacia complex (14 strains), P. aeruginosa (4 strains) and E. coli (3 strains), using ultra-high performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry (UHPLC-ESI-Q-TOF-MS). Multi- and univariate analyses were used to identify specific metabolites in B. pseudomallei.

RESULTS: Principal component and partial-least squares discrimination analysis readily distinguished the metabolomes between B. pseudomallei and other bacterial species. Using multi-variate and univariate analysis, eight metabolites with significantly higher levels in B. pseudomallei were identified. Three of the eight metabolites were identified by MS/MS, while five metabolites were unidentified against database matching, suggesting that they may be potentially novel compounds. One metabolite, m/z 144.048, was identified as 4-methyl-5-thiazoleethanol, a degradation product of thiamine (vitamin B1), with molecular formula C6H9NOS by database searches and confirmed by MS/MS using commercially available authentic chemical standard. Two metabolites, m/z 512.282 and m/z 542.2921, were identified as tetrapeptides, Ile-His-Lys-Asp with molecular formula C22H37N7O7 and Pro-Arg-Arg-Asn with molecular formula C21H39N11O6, respectively. To investigate the high levels of 4-methyl-5-thiazoleethanol in B. pseudomallei, we compared the thiamine degradation pathways encoded in genomes of B. pseudomallei and B. thailandensis. While both B. pseudomallei and B. thailandensis possess thiaminase I which catalyzes degradation of thiamine to 4-methyl-5-thiazoleethanol, thiM, which encodes hydroxyethylthiazole kinase responsible for degradation of 4-methyl-5-thiazoleethanol, is present and expressed in B. thailandensis as detected by PCR/RT-PCR, but absent or not expressed in all B. pseudomallei strains. This suggests that the high 4-methyl-5-thiazoleethanol level in B. pseudomallei is likely due to the absence of hydroxyethylthiazole kinase and hence reduced downstream degradation.

CONCLUSION: Eight novel biomarkers, including 4-methyl-5-thiazoleethanol and two tetrapeptides, were identified in the culture supernatant of B. pseudomallei.

Keywords: Biomarkers; Burkholderia pseudomallei; Metabolomics; Specific

References

  1. J Clin Microbiol. 2003 May;41(5):2068-79 - PubMed
  2. Clin Infect Dis. 2000 Oct;31(4):981-6 - PubMed
  3. J Clin Microbiol. 2014 Apr;52(4):1153-60 - PubMed
  4. PLoS Pathog. 2008 Oct;4(10):e1000178 - PubMed
  5. Bioinformatics. 2008 Dec 1;24(23):2803-4 - PubMed
  6. Am J Trop Med Hyg. 2001 Sep;65(3):177-9 - PubMed
  7. Analyst. 2011 Nov 21;136(22):4752-63 - PubMed
  8. PLoS Genet. 2013;9(9):e1003795 - PubMed
  9. Nat Chem Biol. 2007 Aug;3(8):492-7 - PubMed
  10. Am J Trop Med Hyg. 2006 Nov;75(5):947-54 - PubMed
  11. J Microbiol Methods. 2012 Mar;88(3):419-26 - PubMed
  12. Clin Microbiol Rev. 2005 Apr;18(2):383-416 - PubMed
  13. Emerg Infect Dis. 2009 Nov;15(11):1799-801 - PubMed
  14. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):395-400 - PubMed
  15. J Clin Microbiol. 2012 Sep;50(9):3142-3 - PubMed
  16. Mol Biol Evol. 2011 Oct;28(10):2731-9 - PubMed
  17. Emerg Microbes Infect. 2014 Oct;3(10):e69 - PubMed
  18. Biochemistry. 2008 Feb 5;47(5):1346-57 - PubMed
  19. PLoS Negl Trop Dis. 2011 Sep;5(9):e1303 - PubMed
  20. Anal Chem. 2006 Feb 1;78(3):779-87 - PubMed
  21. Emerg Infect Dis. 2011 Jul;17(7):1296-8 - PubMed
  22. Emerg Infect Dis. 2011 Jul;17(7):1286-8 - PubMed
  23. Nucleic Acids Res. 2013 Jan;41(Database issue):D801-7 - PubMed
  24. Chest. 1975 Aug;68(2):261-3 - PubMed
  25. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D34-8 - PubMed
  26. Appl Environ Microbiol. 2005 Jul;71(7):3917-27 - PubMed
  27. Anal Chem. 2012 Jan 3;84(1):283-9 - PubMed
  28. Emerg Infect Dis. 2005 Jan;11(1):139-40 - PubMed
  29. J Lipid Res. 2009 Apr;50 Suppl:S9-14 - PubMed
  30. PLoS Pathog. 2010 Apr 01;6(4):e1000845 - PubMed
  31. BMC Bioinformatics. 2008 Nov 28;9:504 - PubMed
  32. Nucleic Acids Res. 2012 Jul;40(Web Server issue):W127-33 - PubMed
  33. J Clin Microbiol. 2003 Aug;41(8):3973-7 - PubMed
  34. Infect Immun. 1997 Oct;65(10):4319-21 - PubMed
  35. Curr Opin Infect Dis. 2002 Apr;15(2):127-32 - PubMed
  36. Emerg Infect Dis. 2005 Sep;11(9):1458-60 - PubMed
  37. Southeast Asian J Trop Med Public Health. 2010 Mar;41(2):401-9 - PubMed
  38. Indian J Med Microbiol. 2003 Apr-Jun;21(2):129-32 - PubMed
  39. Anal Chem. 2008 Oct 1;80(19):7562-70 - PubMed
  40. Nucleic Acids Res. 2013 Jan;41(Database issue):D625-30 - PubMed
  41. Am J Trop Med Hyg. 2011 Aug;85(2):282-4 - PubMed
  42. J Clin Microbiol. 2011 Mar;49(3):814-21 - PubMed
  43. PLoS Negl Trop Dis. 2012;6(10):e1871 - PubMed
  44. Clin Infect Dis. 2011 Apr 15;52(8):1024-8 - PubMed
  45. Biochemistry. 1998 Nov 10;37(45):15981-9 - PubMed
  46. J Proteome Res. 2013 Oct 4;12(10):4642-9 - PubMed
  47. J Mass Spectrom. 2010 Jul;45(7):703-14 - PubMed
  48. J Clin Microbiol. 2013 Jan;51(1):334-8 - PubMed
  49. Biochemistry. 2005 Feb 22;44(7):2319-29 - PubMed
  50. Am J Trop Med Hyg. 2012 Jun;86(6):1039-42 - PubMed
  51. J Clin Microbiol. 2006 Dec;44(12):4601-4 - PubMed
  52. Ther Drug Monit. 2005 Dec;27(6):747-51 - PubMed
  53. MBio. 2013 Jul 16;4(4):null - PubMed
  54. Annu Rev Microbiol. 2001;55:165-99 - PubMed
  55. Sci Rep. 2014 Oct 22;4:6728 - PubMed
  56. Mol Cell Probes. 2009 Jun-Aug;23(3-4):178-87 - PubMed
  57. Genome Res. 2011 Jun;21(6):925-35 - PubMed
  58. Diagn Microbiol Infect Dis. 2002 Oct;44(2):143-9 - PubMed
  59. Dis Markers. 2003-2004;19(4-5):169-83 - PubMed
  60. Nucleic Acids Res. 2014 Jan;42(Database issue):D199-205 - PubMed

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