본문 바로가기
KERD
논문KCI 등재

MALDI-TOF MS의 임상검사실 내 적용과 미생물검사의 패러다임 변화

MALDI-TOF MS: Its Application in the Clinical Laboratory and a Paradigm Shift in Clinical Microbiology

박정수|이경훈|김의종|박경운|황상미|송정한|홍윤지|김택수
대한진단검사의학회 (Korean Society For Laboratory Medicine)|2015.10|Laboratory Medicine Online|제5권 제4호|pp. 176-187

2

조회

0

다운로드

2

인용

0

참고문헌

초록

지난 10여 년에 걸쳐, 임상미생물분야는 미생물 동정에 있어 다소 느린 전통적인 동정 알고리즘에서 신속히 결과를 확인할 수 있는 분자진단학적 방법 또는 질량분석법으로의 혁신적인 변화를 겪고 있다. 일찍이, 질량분석법은 임상화학검사실에서의 단백기반 시료 분석법으로 적용되어 왔다. 최근, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) 원리를 이용한 질량분석법이 미생물검사실에 도입되면서 미생물 동정에 있어 신속, 정확한 미생물 동정결과를 제공할 수 있게 되었다. 널리 알려진 제조사의 제품으로 2가지 장비 플랫폼이 기존의 표현형을 통한 동정 자동화 장비를 대체하고 있으며, 일부 경우에서는 염기서열 기반 동정기법 대신으로도 사용되고 있다. 이 종설은 임상연구나 임상미생물검사에 있어 MALDI-TOF 질량분석법의 현재 상황을 요약하고, 시료 처리, 분석 알고리즘, 해석 및 한계를 분석한 최근 연구들을 소개하고자 한다. 또한, 현재 상용화된 MALDI-TOF 질량분석기와 그 분석 소프트웨어에 대해서도 다룰 것이다. 마지막으로, 임상검사실에서 이러한 신규 검사법들의 잠재능력을 개발하기 위해 끊임없이 노력하고 개발자들과의 협력관계를 공고히 한다면 MALDI-TOF 질량분석법을 비롯한 새로운 기술에 있어 향후 진단 분야에서의 용도를 새롭게 정의할 수 있을 것이다.

Abstract

In the past decade, clinical microbiology underwent revolutionary changes in methods used to identify microorganisms, a transition from slow and traditional microbial identification algorithms to rapid molecular methods and mass spectrometry (MS). Earlier, MS was clinically used as a highly complex method that was adapted for protein-centered analysis of samples in chemistry laboratories. Recently, a paradigm-shift happened when matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS was implemented to be used in microbiology laboratories for rapid and robust methods for accurate microbial identification. Two instrument platforms, marketed by well-established manufacturers, are beginning to displace automated phenotypic identification instruments and in some cases even genetic sequence-based identification practices. This review summarizes the current role of MALDI-TOF MS in clinical research, in diagnostic clinical microbiology laboratories, and serves as an introduction to MALDI-TOF MS, highlighting research associated with sample preparation, algorithms, interpretations, and limitations. Currently available MALDI-TOF MS instruments as well as software platforms that support the use of MALDI-TOF with direct specimens have been discussed in this review. Finally, clinical laboratories are consistently striving to extend the potential of these new methods, often in partnership with developmental scientists, resulting in novel technologies, such as MALDI-TOF MS, which could shape and define the diagnostic landscape for years to come.

참고문헌 (50)

  1. Wieser A, "MALDI-TOF MS in microbiological diagnostics-identification of microorganisms and beyond (mini review)", Appl Microbiol Biotechnol, 93, pp.965~974 (2012)
  2. Anhalt JP, "Identification of bacteria using mass spectrometry", Anal Chem, 47, pp.219~225 (1975)
  3. Claydon MA, "The rapid identification of intact microorganisms using mass spectrometry", Nat Biotechnol, 14, pp.1584~1586 (1996)
  4. Jarman KH, "An algorithm for automated bacterial identification using matrix-assisted laser desorption", ionization mass spectrometry, 2000, pp.72, 1217~1223
  5. Sauer S, "Classification and identification of bacteria by mass spectrometry and computational analysis", PLoS One, 3, pp.e2843~ (2008)
  6. Holland RD, "Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption", ionization with time-of-flight mass spectrometry, 1996, pp.10, 1227~1232
  7. Fenselau C, "Characterization of intact microorganisms by MALDI mass spectrometry", Mass Spectrom Rev, 20, pp.157~171 (2001)
  8. Rupf S, "Differentiation of mutans streptococci by intact cell matrix-assisted laser desorption", ionization time-of-flight mass spectrometry, 2005, pp.20, 267~273
  9. Jackson KA, "Optimisation of intact cell MALDI method for fingerprinting of methicillin-resistant Staphylococcus aureus", J Microbiol Methods, 62, pp.273~284 (2005)
  10. Kumar PM, "Rapid discrimination between strains of beta haemolytic streptococci by intact cell mass spectrometry", Indian J Med Res, 119, pp.283~288 (2004)
  11. Hettick JM, "Discrimination of intact mycobacteria at the strain level : a combined MALDI-TOF MS and biostatistical analysis", Proteomics, 6, pp.6416~6425 (2006)
  12. Bizzini A, "Matrix-assisted laser desorption ionization-time of flight mass spectrometry as an alternative to 16S rRNA gene sequencing for identification of difficult-to-identify bacterial strains", J Clin Microbiol, 49, pp.693~696 (2011)
  13. Verroken A, "Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of nocardia species", J Clin Microbiol, 48, pp.4015~4021 (2010)
  14. Drevinek M, "Evaluation of sample preparation methods for MALDI-TOF MS identification of highly dangerous bacteria", Lett Appl Microbiol, 55, pp.40~46 (2012)
  15. El Khéchine A, "Matrix-assisted laser desorption", ionization time-of-flight mass spectrometry identification of mycobacteria in routine clinical practice, 2011, pp.6, e24720~
  16. Patel R, "Matrix-assisted laser desorption ionization-time of flight mass spectrometry in clinical microbiology", Clin Infect Dis, 57, pp.564~572 (2013)
  17. Ferreira L, "Identification of Brucella by MALDI-TOF mass spectrometry. Fast and reliable identification from agar plates and blood cultures", PLoS One, 5, pp.e14235~ (2010)
  18. Moussaoui W, "Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identifies 90% of bacteria directly from blood culture vials", Clin Microbiol Infect, 16, pp.1631~1638 (2010)
  19. Prod’hom G, "Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets", J Clin Microbiol, 48, pp.1481~1483 (2010)
  20. Stevenson LG, "Rapid identification of bacteria in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry", J Clin Microbiol, 48, pp.444~447 (2010)
  21. Wolk DM, "New technologies in clinical microbiology", J Clin Microbiol, 49, pp.s62~s67 (2011)
  22. Klein S, "Integration of matrix-assisted laser desorption", ionization time-of-flight mass spectrometry in blood culture diagnostics : a fast and effective approach, 2012, pp.61, 323~331
  23. Ferreira L, "Direct identification of urinary tract pathogens from urine samples by matrix-assisted laser desorption ionization-time of flight mass spectrometry", J Clin Microbiol, 48, pp.2110~2115 (2010)
  24. Ferreira L, "Rapid method for direct identification of bacteria in urine and blood culture samples by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: intact cell vs. extraction method", Clin Microbiol Infect, 17, pp.1007~1012 (2011)
  25. Fiedler GM, "Standardized peptidome profiling of human urine by magnetic bead separation and matrix-assisted laser desorption", ionization time-of-flight mass spectrometry, 2007, pp.53, 421~428
  26. Thongboonkerd V, "Bacterial overgrowth affects urinary proteome analysis: recommendation for centrifugation, temperature, duration, and the use of preservatives during sample collection", J Proteome Res, 6, pp.4173~4181 (2007)
  27. Köhling HL, "Direct identification of bacteria in urine samples by matrix-assisted laser desorption", ionization time-of-flight mass spectrometry and relevance of defensins as interfering factors, 2012, pp.61, 339~344
  28. Wang XH, "Direct identification of bacteria causing urinary tract infections by combining matrix-assisted laser desorption ionization-time of flight mass spectrometry with UF-1000i urine flow cytometry", J Microbiol Methods, 92, pp.231~235 (2013)
  29. Nyvang Hartmeyer G, "Mass spectrometry : pneumococcal meningitis verified and Brucella species identified in less than half an hour", Scand J Infect Dis, 42, pp.716~718 (2010)
  30. La Scola B, "Intact cell MALDI-TOF mass spectrometry-based approaches for the diagnosis of bloodstream infections", Expert Rev Mol Diagn, 11, pp.287~298 (2011)
  31. La Scola B, "Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry", PLoS One, 4, pp.e8041~ (2009)
  32. Ferroni A, "Real-time identification of bacteria and Candida species in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry", J Clin Microbiol, 48, pp.1542~1548 (2010)
  33. Christner M, "Rapid identification of bacteria from positive blood culture bottles by use of matrix-assisted laser desorption-ionization time of flight mass spectrometry fingerprinting", J Clin Microbiol, 48, pp.1584~1591 (2010)
  34. Friedrichs C, "Rapid identification of viridans streptococci by mass spectrometric discrimination", J Clin Microbiol, 45, pp.2392~2397 (2007)
  35. Szabados F, "The sensitivity of direct identification from positive BacT", ALERT ™(bioMérieux)blood culture bottles by matrix-assisted laser desorption ionization time-of-flight mass spectrometry is low, 2011, pp.17, 192~195
  36. Vlek AL, "Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry improves appropriateness of antibiotic treatment of bacteremia", PLoS One, 7, pp.e32859~ (2012)
  37. Chen JH, "Direct bacterial identification in positive blood cultures by use of two commercial matrix-assisted laser desorption ionization-time of flight mass spectrometry systems", J Clin Microbiol, 51, pp.1733~1739 (2013)
  38. Marinach-Patrice C, "Rapid species diagnosis for invasive candidiasis using mass spectrometry", PLoS One, 5, pp.e8862~ (2010)
  39. Spanu T, "Direct maldi-tof mass spectrometry assay of blood culture broths for rapid identification of Candida species causing bloodstream infections : an observational study in two large microbiology laboratories", J Clin Microbiol, 50, pp.176~179 (2012)
  40. La Scola B, "Burden of emerging anaerobes in the MALDI-TOF and 16S rRNA gene sequencing era", Anaerobe, 17, pp.106~112 (2011)
  41. Munoz R, "Evaluation of matrix-assisted laser desorption ionization-time of flight whole cell profiles for assessing the cultivable diversity of aerobic and moderately halophilic prokaryotes thriving in solar saltern sediments", Syst Appl Microbiol, 34, pp.69~75 (2011)
  42. Schleifer KH, "Transfer of Streptococcus lactis and Related Streptococci to the Genus Lactococcus gen. nov", Syst Appl Microbiol, 6, pp.183~195 (1985)
  43. Welker M, "Applications of whole-cell matrix-assisted laser-desorption", ionization time-of-flight mass spectrometry in systematic microbiology, 2011, pp.34, 2~11
  44. Gabriel SB, "The structure of haplotype blocks in the human genome", Science, 296, pp.2225~2229 (2002)
  45. Sauer S, "Single-nucleotide polymorphisms : analysis by mass spectrometry", Nat Protoc, 1, pp.1761~1771 (2006)
  46. Stuyver L, "Line probe assay for monitoring drug resistance in hepatitis B virus-infected patients during antiviral therapy", J Clin Microbiol, 38, pp.702~707 (2000)
  47. Stuyver L, "Second-generation line probe assay for hepatitis C virus genotyping", J Clin Microbiol, 34, pp.2259~2266 (1996)
  48. Kim HS, "Evaluation of methods for monitoring drug resistance in chronic hepatitis B patients during lamivudine therapy based on mass spectrometry and reverse hybridization", Antivir Ther, 10, pp.441~449 (2005)
  49. Hong SP, "Detection of hepatitis B virus YMDD variants using mass spectrometric analysis of oligonucleotide fragments", J Hepatol, 40, pp.837~844 (2004)
  50. Kim YJ, "Population genotyping of hepatitis C virus by matrix-assisted laser desorption", ionization time-of-flight mass spectrometry analysis of short DNA fragments, 2005, pp.51, 1123~1131

관련 논문AI추천

Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry의 활용권필승대한임상검사과학회 · 대한임상검사과학회지2023 · 제55권 제4호Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry in Clinical Microbiology: What Are the Current Issues?Alex van Belkum, David Pincus, Jean-Philippe Charrier, Martin Welker, Victoria Girard대한진단검사의학회 · Annals of Laboratory Medicine2017 · 제37권 제6호임상미생물 검사실에서 산소성 세균 동정을 위한 Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry의 유용성권미정, 김명숙, 용동은, 이경원, 이양순, 정석훈, 정윤섭, 정혜선대한임상미생물학회 · Annals of Clinical Microbiology2012 · 제15권 제2호Clinical efficacy of matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry in patients with multidrug-resistant bacteremia: a single-center study in Korea김기욱, 김미현, 목정하, 박혜경, 엄중섭, 이광하, 이민기, 조은정대한내과학회 · The Korean Journal of Internal Medicine2019 · 제34권 제5호새로운 말디토프 질량 분석 장비인 ASTA MicroIDSys의 임상 균주를 이용한 균종 동정 성능 평가김도균, 유창승, 이은정, 정석훈대한임상미생물학회 · Annals of Clinical Microbiology2020 · 제23권 제3호Comparison of a New Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Platform, ASTA MicroIDSys, With Bruker Biotyper for Species Identification김현수, 성지연, 용동은, 이경원, 이양순대한진단검사의학회 · Annals of Laboratory Medicine2017 · 제37권 제6호

이 간행물의 다른 논문 (9건)

차세대 신생아 선별검사에 대한 전망김종원, 박경진pp. 169-175자동혈구분석기 Sysmex XN-2000의 성능 및 Low WBC Mode를 이용한 백혈구 감별계산 정확성 평가이정녀, 전경란, 송새암, 이자영, 김혜란, 신정환, 오승환pp. 188-195한국에서 탠덤 질량분석기를 이용한 선천성 대사이상질환 신생아 선별검사: 일 개 전문 수탁기관의 경험이인범, 박은정, 이현주, 서동희, 오정민, 조대연, 조성은pp. 196-203선별 소변검사의 단백과 비중을 결합한 검사지표의 평가박일규, 한송희pp. 204-210폼페병의 진단 및 치료효과 확인을 위한 초고성능 액체크로마토그래피-탠덤질량분석기를 이용한 소변 포도당 사당류(Glc4) 측정법의 평가전선희, 송상훈, 이경훈, 박경운, 송정한, 박형두, 남영원pp. 211-214
원문 보기