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The Use of Microbial Metabolites for the Diagnosis of Infectious Diseases

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Advanced Techniques in Diagnostic Microbiology

Abstract

Volatile organic compounds (VOCs) produced by microbes through their primary and secondary metabolism can be used to identify infections caused by these organisms. The detection of microbial VOCs in human breath allows noninvasive, rapid, species-specific diagnosis of these infections. However, the detection and identification of these microbe-specific breath VOC signatures are still quite challenging due to the very low abundance of microbial VOCs in human breath. Pre-concentration of these VOCs, which are highly diluted in human breath, is important for the evaluation of these metabolites. In this chapter, we discuss methods for pre-concentration of VOCs using sorbent materials, solid-phase microextraction, and headspace sorptive extraction, and review common analytical techniques used to analyze breath VOCs, such as gas chromatography-mass spectrometry, soft ionization mass spectrometry techniques, ion mobility spectrometry, differential mobility spectrometry, and electronic nose sensors.

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References

  1. Richard Hung JWBSUM. Volatile affairs in microbial interactions. ISME J. 2015;9:2329–35.

    Article  Google Scholar 

  2. Morath SU, Hung R, Bennett JW. Fungal volatile organic compounds : a review with emphasis on their biotechnological potential. Fungal Biol Rev. 2012;26:73–83.

    Article  Google Scholar 

  3. Schmidt R, Jager VDe, Zühlke D, Wolff C, Bernhardt J, Cankar K, Beekwilder J, Ijcken WV, Sleutels F, Boer WD, Riedel K, Garbeva P. Fungal volatile compounds induce production of the secondary metabolite Sodorifen in Serratia plymuthica PRI-2C. Nature Scientific Reports 2017;7(862):1–14.

    Google Scholar 

  4. Korpi A, Järnberg J, Pasanen A-L. Microbial volatile organic compounds. Crit Rev Toxicol. 2009;39:139–93.

    Article  CAS  Google Scholar 

  5. Frisvad JC, Andersen B, Thrane U. The use of secondary metabolite profiling in chemotaxonomy of filamentous fungi. Mycol Res. 2008;112:231–40.

    Article  CAS  Google Scholar 

  6. Keller NP, Turner G, Bennett JW. Fungal secondary metabolism – from biochemistry to genomics. Nat Rev Microbiol. 2005;3:937–47.

    Article  CAS  Google Scholar 

  7. Donadio S, McAlpine JB, Sheldon PJ, Jackson M, Katz L. An erythromycin analog produced by reprogramming of polyketide synthesis. Proc Natl Acad Sci. 1993;90:7119–23.

    Article  CAS  Google Scholar 

  8. Krukemyer JJ, Talbert RL. Lovastatin: a new cholesterol-lowering agent. J Hum Pharmacol Drug Ther. 2012;7:198.

    Article  Google Scholar 

  9. Asadollahi MA, Maury J, Schalk M, Clark A, Nielsen J. Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the Mevalonate pathway in Saccharomyces Cerevisiae. Biotechnol Bioeng. 2010;106:86–96.

    CAS  PubMed  Google Scholar 

  10. Scalcinati G, Knuf C, Partow S, Chen Y, Maury J, Schalk M, Daviet L, Nielsen J, Siewers V. Dynamic control of gene expression in Saccharomyces cerevisiae engineered for the production of plant sesquitepene α-santalene in a fed-batch mode. Metab Eng. 2012;14:91–103.

    Article  CAS  Google Scholar 

  11. Koo S, Thomas HR, Daniels SD, Lynch RC, Fortier SM, Shea MM, Rearden P, Comolli JC, Baden LR, Marty FM. A breath fungal secondary metabolite signature to diagnose invasive aspergillosis. Clin Infect Dis. 2014;59:1733–40.

    Article  CAS  Google Scholar 

  12. Bazemore RA, Feng J, Cseke L, Podila GK. Biomedically important pathogenic fungi detection with volatile biomarkers. J Breath Res. 2012;6:16002.

    Article  CAS  Google Scholar 

  13. Lin HC, Chooi YH, Dhingra S, Xu W, Calvo AM, Tang Y. The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic Terpene cyclase involved in the formation of ??-trans-bergamotene. J Am Chem Soc. 2013;135:4616–9.

    Article  CAS  Google Scholar 

  14. Sethi S, Nanda R, Chakraborty T. Clinical application of volatile organic compound analysis for detecting infectious diseases. Clin Microbiol Rev. 2013;26:462–75.

    Article  CAS  Google Scholar 

  15. Thalavitiya Acharige MJ, Koshy S, Ismail N, Aloum O, Jazaerly M, Leon Astudillo C, Koo S. J. Breath Res. 2018;12:027108.

    Google Scholar 

  16. Wang C, Sahay P. Breath analysis using laser spectroscopic techniques: breath biomarkers, spectral fingerprints, and detection limits. Sensors. 2009;9:8230–62.

    Article  CAS  Google Scholar 

  17. Gong, X, Shi S, Gamez G. Real-time quantitative analysis of valproic acid in exhaled breath by low temperature plasma ionization mass spectrometry. J Am Soc Mass Spectrom. 2017;28(4):678–87.

    Article  Google Scholar 

  18. Koshy S, Ismail N, Astudillo CL, Haeger CM, Aloum O, Acharige MT, Farmakiotis D, Baden LR, Marty FM, Kontoyiannis DP, et al. Breath-based diagnosis of Invasive Mucormycosis (IM). In: IDWeek. San Diego: Oxford University Press; 2017.

    Google Scholar 

  19. Zhu J, Bean HD, Wargo MJ, Leclair LW, Hill JE. Detecting bacterial lung infections: in vivo evaluation of in vitro volatile fingerprints. J Breath Res. 2013;7:16003.

    Article  Google Scholar 

  20. Scott-Thomas AJ, Syhre M, Pattemore PK, Epton M, Laing R, Pearson J, Chambers ST. 2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung. BMC Pulm Med. 2010;10:56.

    Article  Google Scholar 

  21. Shestivska V, Nemec A, Dřevínek P, Sovová K, Dryahina K, Spaněl P. Quantification of methyl thiocyanate in the headspace of Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis patients by selected ion flow tube mass spectrometry. Rapid Commun Mass Spectrom. 2011;25:2459–67.

    Article  CAS  Google Scholar 

  22. Carterson AJ, Morici LA, Jackson DW, Frisk A, Lizewski SE, Jupiter R, Kunz DA, Davis SH, Schurr JR, Hassett DJ, et al. The transcriptional regulator AlgR controls cyanide production in Pseudomonas aeruginosa. J Bacteriol. 2004;186:6837–44.

    Article  CAS  Google Scholar 

  23. Chambers ST, Syhre M, Murdoch DR, McCartin F, Epton MJ. Detection of 2-Pentylfuran in the breath of patients with Aspergillus fumigatus. Med Mycol. 2009;47:468–76.

    Article  CAS  Google Scholar 

  24. Larsen TO, Frisvad JC. Comparison of different methods for collection of volatile chemical markers from fungi. J Microbiol Methods. 1995;24:135–44.

    Article  CAS  Google Scholar 

  25. Benoit FM, Davidson WR, Lovett AM, Nacson S, Ngo A. Breath analysis by atmospheric pressure ionization mass spectrometry. Anal Chem. 1983;55:805–7.

    Article  CAS  Google Scholar 

  26. Fiedler K, Schütz E, Geh S. Detection of microbial volatile organic compounds (MVOCs) produced by moulds on various materials. Int J Hyg Environ Health. 2001;204:111–21.

    Article  CAS  Google Scholar 

  27. Chambers ST, Bhandari S, Scott-Thomas A, Syhre M. Novel diagnostics: progress toward a breath test for invasive Aspergillus fumigatus. Med Mycol Off Publ Int Soc Hum Anim Mycol. 2011;49(Suppl 1):S54–61.

    CAS  Google Scholar 

  28. Wihlborg R, Pippitt D, Marsili R. Headspace Sorptive extraction and GC-TOFMS for the identification of volatile fungal metabolites. J Microbiol Methods. 2008;75:244–50.

    Article  CAS  Google Scholar 

  29. Bicchi C, Iori C, Rubiolo P, Sandra P. Headspace sorptive extraction (HSSE), stir bar Sorptive extraction (SBSE), and solid phase microextraction (SPME) applied to the analysis of roasted arabica coffee and coffee brew. J Agric Food Chem. 2002;50:449–59.

    Article  CAS  Google Scholar 

  30. Poli D, Goldoni M, Corradi M, Acampa O, Carbognani P, Internullo E, Casalini A, Mutti A. Determination of aldehydes in exhaled breath of patients with lung Cancer by means of on-fiber-derivatisation SPME-GC/MS. J Chromatogr B Anal Technol Biomed Life Sci. 2010;878:2643–51.

    Article  CAS  Google Scholar 

  31. Song G, Qin T, Liu H, Xu G-B, Pan Y-Y, Xiong F-X, Gu K-S, Sun G-P, Chen Z-D. Quantitative breath analysis of volatile organic compounds of lung Cancer patients. Lung Cancer. 2010;67:227–31.

    Article  Google Scholar 

  32. Li J, Peng Y, Liu Y, Li W, Jin Y, Tang Z, Duan Y. Investigation of potential breath biomarkers for the early diagnosis of breast Cancer using gas chromatography-mass spectrometry. Clin Chim Acta. 2014;436:59–67.

    Article  CAS  Google Scholar 

  33. Gaugg MT, Gomez DG, Barrios-Collado C, Vidal-de-Miguel G, Kohler M, Zenobi R, Martinez-Lozano Sinues P. Expanding metabolite coverage of real-time breath analysis by coupling a universal secondary electrospray ionization source and high resolution mass spectrometry – a pilot study on tobacco smokers. J Breath Res. 2016;10:16010.

    Article  Google Scholar 

  34. Smith D, Španěl P, Herbig J, Beauchamp J. Mass spectrometry for real-time quantitative breath analysis. J Breath Res. 2014;8:27101.

    Article  Google Scholar 

  35. Scotter JM, Langford VS, Wilson PF, McEwan MJ, Chambers ST. Real-time detection of common microbial volatile organic compounds from medically important fungi by Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS). J Microbiol Methods. 2005;63:127–34.

    Article  CAS  Google Scholar 

  36. Smith D, Španěl P. Direct, rapid quantitative analyses of BVOCs using SIFT-MS and PTR-MS obviating sample collection. TrAC – Trends Anal Chem. 2011;30:945–59.

    Article  CAS  Google Scholar 

  37. Allardyce RA, Langford VS, Hill AL, Murdoch DR. Detection of volatile metabolites produced by bacterial growth in blood culture media by selected ion flow tube mass spectrometry (SIFT-MS). J Microbiol Methods. 2006;65:361–5.

    Article  CAS  Google Scholar 

  38. Smith D, Španěl P. Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis. Mass Spectrom Rev. 2005;24:661–700.

    Article  CAS  Google Scholar 

  39. Miekisch W, Schubert JK. From highly sophisticated analytical techniques to life-saving diagnostics: technical developments in breath analysis. TrAC – Trends Anal Chem. 2006;25:665–73.

    Article  CAS  Google Scholar 

  40. Biasioli F, Gasperi F, Yeretzian C, Märk T. D. PTR-MS monitoring of VOCs and BVOCs in food science and technology. TrAC – Trends Anal Chem. 2011;30:968–77.

    Article  CAS  Google Scholar 

  41. Biasioli F, Yeretzian C, Märk TD, Dewulf J, van Langenhove H. Direct-injection mass spectrometry adds the time dimension to (B)VOC analysis. TrAC – Trends Anal Chem. 2011;30:1003–17.

    Article  CAS  Google Scholar 

  42. Kohl I, Beauchamp J, Cakar-Beck F, Herbig J, Dunkl J, Tietje O, Tiefenthaler M, Boesmueller C, Wisthaler A, Breitenlechner M, et al. First observation of a potential non-invasive breath gas biomarker for kidney function. J Breath Res. 2013;7:17110.

    Article  Google Scholar 

  43. Handa H, Usuba A, Maddula S, Baumbach JI, Mineshita M, Miyazawa T. Exhaled breath analysis for lung cancer detection using ion mobility spectrometry. PLoS One. 2014;9:e114555.

    Article  Google Scholar 

  44. Vautz W, Nolte J, Fobbe R, Baumbach JI. Breath analysis – performance and potential of ion mobility spectrometry. J Breath Res. 2009;3:36004.

    Article  Google Scholar 

  45. Fink T, Baumbach JI, Kreuer S. Ion mobility spectrometry in breath research. J Breath Res. 2014;8:27104.

    Article  Google Scholar 

  46. Westhoff M, Litterst P, Freitag L, Urfer W, Bader S, Baumbach J-I. Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of patients with lung cancer: results of a pilot study. Thorax. 2009;64:744–8.

    Article  CAS  Google Scholar 

  47. Mäkinen MA, Anttalainen OA, Sillanpää MET. Ion mobility spectrometry and its applications in detection of chemical warfare agents. Anal Chem. 2010;82:9594–600.

    Article  Google Scholar 

  48. Cao L, Harrington PDB, Liu C. Two-dimensional nonlinear wavelet compression of ion mobility spectra of chemical warfare agent simulants. Anal Chem. 2004;76:2859–68.

    Article  CAS  Google Scholar 

  49. Eiceman GA, Krylov EV, Krylova NS, Nazarov EG, Miller RA. Separation of ions from explosives in differential mobility spectrometry by vapor-modified drift gas. Anal Chem. 2004;76:4937–44.

    Article  CAS  Google Scholar 

  50. Lambertus GR, Fix CS, Reidy SM, Miller RA, Wheeler D, Nazarov E, Sacks R. Silicon microfabricated column with microfabricated differential mobility spectrometer for GC analysis of volatile organic compounds. Anal Chem. 2005;77:7563–71.

    Article  CAS  Google Scholar 

  51. Kolakowski BM, Mester Z. Review of applications of high-field asymmetric waveform ion mobility spectrometry (FAIMS) and differential mobility spectrometry (DMS). Analyst. 2007;132:842–64.

    Article  CAS  Google Scholar 

  52. Eiceman GA, Krylov EV, Tadjikov B, Ewing RG, Nazarov EG, Miller RA. Differential mobility spectrometry of chlorocarbons with a micro-fabricated drift tube. Analyst. 2004;129:297–304.

    Article  CAS  Google Scholar 

  53. Turner APF, Magan N. Innovation: electronic noses and disease diagnostics. Nat Rev Microbiol. 2004;2:161–6.

    Article  CAS  Google Scholar 

  54. Zhang Y, Askim JR, Zhong W, Orlean P, Suslicka KS. Identification of pathogenic fungi with an optoelectronic nose. Biophys Chem. 2005;257:2432–7.

    Google Scholar 

  55. De Heer K, Van Der Schee MP, Zwinderman K, Van Den Berk IAH, Visser CE, Van Oers R, Sterk PJ. Electronic nose technology for detection of invasive pulmonary Aspergillosis in prolonged chemotherapy-induced neutropenia: a proof-of-principle study. J Clin Microbiol. 2013;51:1490–5.

    Article  Google Scholar 

  56. Casalinuovo IA, Di Pierro D, Coletta M, Di Francesco P. Application of electronic noses for disease diagnosis and food spoilage detection. Sensors. 2006;6:1428–39.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA, USA

    Mahesh J. Thalavitiya Acharige, Seena S. Koshy & Sophia Koo

  2. Harvard Medical School, Boston, MA, USA

    Mahesh J. Thalavitiya Acharige, Seena S. Koshy & Sophia Koo

  3. Dana-Farber Cancer Institute, Boston, MA, USA

    Sophia Koo

Authors
  1. Mahesh J. Thalavitiya Acharige
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  2. Seena S. Koshy
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  3. Sophia Koo
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Correspondence to Sophia Koo .

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Editors and Affiliations

  1. Departments of Laboratory Medicine and Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Yi-Wei Tang

  2. Department of Pathology, Microbiology and Immunology and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Charles W. Stratton

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Thalavitiya Acharige, M.J., Koshy, S.S., Koo, S. (2018). The Use of Microbial Metabolites for the Diagnosis of Infectious Diseases. In: Tang, YW., Stratton, C. (eds) Advanced Techniques in Diagnostic Microbiology. Springer, Cham. https://doi.org/10.1007/978-3-319-33900-9_12

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