User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Rapid Etiological Classification of Meningitis by NMR Spectroscopy Based on Metabolite Profiles and Host Response

Primary tabs

download
  • Open access
  • PDF
  • 170.94 K
Himmelreich, Uwe [The University of Sydney, Australia] Malik, Richard [The University of Sydney, Australia] Kuhn, Till [Bruker Biospin, Switzerland] Daniel, Heide-Marie [UCL] Somorjai, Ray L [Institute for Biodiagnostics, Canada] Sorrell, Tania C [The University of Sydney, Australia]

Bacterial meningitis is an acute disease with high mortality that is reduced by early treatment. Identification of the causative microorganism by culture is sensitive but slow. Large volumes of cerebrospinal fluid (CSF) are required to maximise sensitivity and establish a provisional diagnosis. We have utilised nuclear magnetic resonance (NMR) spectroscopy to rapidly characterise the biochemical profile of CSF from normal rats and animals with pneumococcal or cryptococcal meningitis. Use of a miniaturised capillary NMR system overcame limitations caused by small CSF volumes and low metabolite concentrations. The analysis of the complex NMR spectroscopic data by a supervised statistical classification strategy included major, minor and unidentified metabolites. Reproducible spectral profiles were generated within less than three minutes, and revealed differences in the relative amounts of glucose, lactate, citrate, amino acid residues, acetate and polyols in the three groups. Contributions from microbial metabolism and inflammatory cells were evident. The computerised statistical classification strategy is based on both major metabolites and minor, partially unidentified metabolites. This data analysis proved highly specific for diagnosis (100% specificity in the final validation set), provided those with visible blood contamination were excluded from analysis; 6-8% of samples were classified as indeterminate. This proof of principle study suggests that a rapid etiologic diagnosis of meningitis is possible without prior culture. The method can be fully automated and avoids delays due to processing and selective identification of specific pathogens that are inherent in DNA-based techniques.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2009
Language Anglais
Journal information "PLoS One" - Vol. 4, no. 4, p. E5328 (2009)
Peer reviewed yes
issn 1932-6203
e-issn 1932-6203
Publication status Publié
Affiliation UCL - AGRO/CABI - Département de chimie appliquée et des bio-industries
Keywords 3145
Links
  1. Aronin Steven I., Community-Acquired Bacterial Meningitis: Risk Stratification for Adverse Clinical Outcome and Effect of Antibiotic Timing, 10.7326/0003-4819-129-11_part_1-199812010-00004
  2. Lu Cheng-Hsien, Huang Chi-Ren, Chang Wen-Neng, Chang Chin-Jung, Cheng Ben-Chung, Lee Ping-Yu, Lin Mei-Wen, Chang Hsueh-Wen, Community-acquired bacterial meningitis in adults: the epidemiology, timing of appropriate antimicrobial therapy, and prognostic factors, 10.1016/s0303-8467(02)00052-5
  3. AR Tunkel, 959 (2000)
  4. de Gans Jan, van de Beek Diederik, Dexamethasone in Adults with Bacterial Meningitis, 10.1056/nejmoa021334
  5. R Fishman (1992)
  6. van de Beek Diederik, de Gans Jan, Spanjaard Lodewijk, Weisfelt Martijn, Reitsma Johannes B., Vermeulen Marinus, Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis, 10.1056/nejmoa040845
  7. M Wood (1998)
  8. Coen M., O'Sullivan M., Bubb W. A., Kuchel P. W., Sorrell T., Proton Nuclear Magnetic Resonance--Based Metabonomics for Rapid Diagnosis of Meningitis and Ventriculitis, 10.1086/497836
  9. Mariey L., Signolle J.P., Amiel C., Travert J., Discrimination, classification, identification of microorganisms using FTIR spectroscopy and chemometrics, 10.1016/s0924-2031(01)00113-8
  10. U Himmelreich, Trends Appl Spectrosc, 5, 269 (2004)
  11. Maquelin K, Kirschner C, Choo-Smith L.-P, van den Braak N, Endtz H.Ph, Naumann D, Puppels G.J, Identification of medically relevant microorganisms by vibrational spectroscopy, 10.1016/s0167-7012(02)00127-6
  12. Fenselau Catherine, Demirev Plamen A., Characterization of intact microorganisms by MALDI mass spectrometry, 10.1002/mas.10004
  13. Allen Jess, Davey Hazel M, Broadhurst David, Heald Jim K, Rowland Jem J, Oliver Stephen G, Kell Douglas B, High-throughput classification of yeast mutants for functional genomics using metabolic footprinting, 10.1038/nbt823
  14. Oliver Stephen G., Raamsdonk Léonie M., Teusink Bas, Broadhurst David, Zhang Nianshu, Hayes Andrew, Walsh Michael C., Berden Jan A., Brindle Kevin M., Kell Douglas B., Rowland Jem J., Westerhoff Hans V., van Dam Karel, 10.1038/83496
  15. Dunn Warwick B., Bailey Nigel J. C., Johnson Helen E., Measuring the metabolome: current analytical technologies, 10.1039/b418288j
  16. Himmelreich U., Somorjai R. L., Dolenko B., Lee O. C., Daniel H.-M., Murray R., Mountford C. E., Sorrell T. C., Rapid Identification of Candida Species by Using Nuclear Magnetic Resonance Spectroscopy and a Statistical Classification Strategy, 10.1128/aem.69.8.4566-4574.2003
  17. Pope Georgina A., MacKenzie Donald A., Defernez Marianne, Aroso Miguel A. M. M., Fuller Linda J., Mellon Fred A., Dunn Warwick B., Brown Marie, Goodacre Royston, Kell Douglas B., Marvin Marcus E., Louis Edward J, Roberts Ian N., Metabolic footprinting as a tool for discriminating between brewing yeasts, 10.1002/yea.1499
  18. Urbanczyk-Wochniak Ewa, Luedemann Alexander, Kopka Joachim, Selbig Joachim, Roessner-Tunali Ute, Willmitzer Lothar, Fernie Alisdair R, Parallel analysis of transcript and metabolic profiles: a new approach in systems biology, 10.1038/sj.embor.embor944
  19. JK Nicholson, 449 (1989)
  20. HIRAOKA Atsushi, MIURA Isao, HATTORI Munekazu, TOMINAGA Itaru, KUSHIDA Katsuhiko, MAEDA Masaakira, Proton Magnetic Resonance Spectroscopy of Cerebrospinal Fluid as an Aid in Neurological Diagnosis., 10.1248/bpb.17.1
  21. Nicoli F., Vion-Dury J., Maloteaux J.M., Delwaide C., Confort-Gouny S., Sciaky M., Cozzone P.J., CSF and serum metabolic profile of patients with Huntington's chorea: A study by high resolution proton NMR spectroscopy and HPLC, 10.1016/0304-3940(93)90168-k
  22. RA Wevers, Clin Chem, 41, 744 (1995)
  23. Hu Yan, Malone James P., Fagan Anne M., Townsend R. Reid, Holtzman David M., Comparative Proteomic Analysis of Intra- and Interindividual Variation in Human Cerebrospinal Fluid, 10.1074/mcp.m500207-mcp200
  24. Selle Hartmut, Lamerz Jens, Buerger Katharina, Dessauer Andreas, Hager Klaus, Hampel Harald, Karl Johann, Kellmann Markus, Lannfelt Lars, Louhija Jukka, Riepe Matthias, Rollinger Wolfgang, Tumani Hayrettin, Schrader Michael, Zucht Hans-Dieter, Identification of Novel Biomarker Candidates by Differential Peptidomics Analysis of Cerebrospinal Fluid in Alzheimers Disease, 10.2174/138620705774962391
  25. Dekker Lennard J., Boogerd Willem, Stockhammer Guenther, Dalebout Johannes C., Siccama Ivar, Zheng Pingpin, Bonfrer Johannes M., Verschuuren Jan J., Jenster Guido, Verbeek Marcel M., Luider Theo M., Smitt Peter A. Sillevis, MALDI-TOF Mass Spectrometry Analysis of Cerebrospinal Fluid Tryptic Peptide Profiles to Diagnose Leptomeningeal Metastases in Patients with Breast Cancer, 10.1074/mcp.m500081-mcp200
  26. GE Pfyffer, J Clin Microbiol, 34, 834 (1996)
  27. Lewczuk Piotr, Esselmann Hermann, Meyer Markus, Wollscheid Volker, Neumann Manuela, Otto Markus, Maler Juan Manuel, Rüther Eckart, Kornhuber Johannes, Wiltfang Jens, The amyloid-β(Aβ) peptide pattern in cerebrospinal fluid in Alzheimer's disease: evidence of a novel carboxyterminally elongated Aβpeptide : Amyloid peptide pattern in AD-CSF by SELDI-TOFMS, 10.1002/rcm.1048
  28. Yuan Xianglin, Desiderio Dominic M., Human cerebrospinal fluid peptidomics, 10.1002/jms.737
  29. Maillet Serge, Vion-Dury Jean, Confort-Gouny Sylviane, Nicoli François, Lutz Norbert W., Viout Patrick, Cozzone Patrick J., Experimental protocol for clinical analysis of cerebrospinal fluid by high resolution proton magnetic resonance spectroscopy, 10.1016/s1385-299x(98)00033-6
  30. Bell Jimmy D., Brown Judith C. C., Sadler Peter J., MacLeod Andrew F., Sönksen Peter H., Hughes Robin D., Williams Roger, High resolution proton nuclear magnetic resonance studies of human cerebrospinal fluid, 10.1042/cs0720563
  31. J Levine, J Transm, 107, 843 (2000)
  32. Griffin Julian L., Nicholls Andrew W., Keun Hector C., Mortishire-Smith Russell J., Nicholson Jeremy K., Kuehn Till, Metabolic profiling of rodent biological fluids via 1H NMR spectroscopy using a 1 mm microlitre probe, 10.1039/b201207c
  33. Schlotterbeck Götz, Ross Alfred, Hochstrasser Remo, Senn Hans, Kühn Till, Marek Daniel, Schett Oscar, High-Resolution Capillary Tube NMR. A Miniaturized 5-μL High-Sensitivity TXI Probe for Mass-Limited Samples, Off-Line LC NMR, and HT NMR, 10.1021/ac025556e
  34. Nikulin Alexander E., Dolenko Brion, Bezabeh Tedros, Somorjai Ray L., Near-optimal region selection for feature space reduction: novel preprocessing methods for classifying MR spectra, 10.1002/(sici)1099-1492(199806/08)11:4/5<209::aid-nbm510>3.0.co;2-5
  35. Himmelreich Uwe, Accurso Richard, Malik Richard, Dolenko Brion, Somorjai Rajmund L., Gupta Rakesh K., Gomes Lavier, Mountford Carolyn E., Sorrell Tania C., Identification ofStaphylococcus aureusBrain Abscesses: Rat and Human Studies with1H MR Spectroscopy, 10.1148/radiol.2361040869
  36. Himmelreich Uwe, Dzendrowskyj Theresa E., Allen Chris, Dowd Susan, Malik Richard, Shehan B. Philip, Russell Peter, Mountford Carolyn E., Sorrell Tania C., Cryptococcomas Distinguished from Gliomas with MR Spectroscopy: An Experimental Rat and Cell Culture Study, 10.1148/radiology.220.1.r01jl25122
  37. Dunne Victoria G., Bhattachayya Shermina, Besser Michael, Rae Caroline, Griffin Julian L., Metabolites from cerebrospinal fluid in aneurysmal subarachnoid haemorrhage correlate with vasospasm and clinical outcome: a pattern-recognition1H NMR study, 10.1002/nbm.918
  38. HG Schlegel (1992)
  39. Himmelreich Uwe, Allen Chris, Dowd Susan, Malik Richard, Shehan B.Philip, Mountford Carolyn, Sorrell Tania C., Identification of metabolites of importance in the pathogenesis of pulmonary cryptococcoma using nuclear magnetic resonance spectroscopy, 10.1016/s1286-4579(03)00028-5
  40. Subramanian Arunachalam, Gupta Abhishek, Saxena Swapnil, Gupta Ashish, Kumar Raj, Nigam Anjali, Kumar Rashmi, Mandal Sudhir K., Roy Raja, Proton MR CSF analysis and a new software as predictors for the differentiation of meningitis in children, 10.1002/nbm.944
  41. AG Palmer III, J Magn Reson, 93, 151 (1991)
  42. RL Somorjai, 67 (2004)
  43. Somorjai R.L., Dolenko B., Nikulin A., Nickerson P., Rush D., Shaw A., Glogowski M., Rendell J., Deslauriers R., Distinguishing normal from rejecting renal allografts: application of a three—stage classification strategy to MR and IR spectra of urine, 10.1016/s0924-2031(01)00148-5
  44. Efron Bradley, Tibshirani Robert J., An Introduction to the Bootstrap, ISBN:9780412042317, 10.1007/978-1-4899-4541-9
Bibliographic reference Himmelreich, Uwe ; Malik, Richard ; Kuhn, Till ; Daniel, Heide-Marie ; Somorjai, Ray L ; et. al. Rapid Etiological Classification of Meningitis by NMR Spectroscopy Based on Metabolite Profiles and Host Response. In: PLoS One, Vol. 4, no. 4, p. E5328 (2009)
Permanent URL http://hdl.handle.net/2078.1/73365