Skip to main content
Log in

MALDI-TOF MS in microbiological diagnostics—identification of microorganisms and beyond (mini review)

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Few developments in microbiological diagnostics have had such a rapid impact on species level identification of microorganisms as matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Conventional differentiation methods rely on biochemical criteria and require additional pre-testing and lengthy incubation procedures. In comparison, MALDI-TOF MS can identify bacteria and yeast within minutes directly from colonies grown on culture plates. This radically new, methodically simple approach profoundly reduces the cost of consumables and time spent on diagnostics. The reliability and accuracy of the method have been demonstrated in numerous studies and different systems are already commercially available. Novel applications of the system besides microbial species level identification are also being explored. This includes identification of pathogens from positive blood cultures or directly from patient samples, such as urine. Currently, intriguing MALDI-TOF MS developments are being made regarding the phenotypic detection of certain antibiotic resistance mechanisms, e.g., β-lactamases and carbapenemases. This mini review provides an overview of the literature in the field and also includes our own data and experiences gathered from over 4 years of routine MALDI-TOF MS use in a university hospital’s microbiological diagnostics facility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Amiri-Eliasi B, Fenselau C (2001) Characterization of protein biomarkers desorbed by MALDI from whole fungal cells. Anal Chem 73(21):5228–5231

    Article  CAS  Google Scholar 

  • Anhalt JP, Fenselau C (1975) Identification of bacteria using mass spectrometry. Anal Chem 47:219–225

    Article  CAS  Google Scholar 

  • Barbuddhe SB, Maier T, Schwarz G, Kostrzewa M, Hof H, Domann E, Chakraborty T, Hain T (2008) Rapid identification and typing of listeria species by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Appl Environ Microbiol 74(17):5402–5407

    Article  CAS  Google Scholar 

  • Bernardo K, Pakulat N, Macht M, Krut O, Seifert H, Fleer S, Hunger F, Kronke M (2002) Identification and discrimination of Staphylococcus aureus strains using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Proteomics 2(6):747–753

    Article  CAS  Google Scholar 

  • Bizzini A, Durussel C, Bille J, Greub G, Prod’hom G (2010) Performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of bacterial strains routinely isolated in a clinical microbiology laboratory. J Clin Microbiol 48(5):1549–1554

    Article  CAS  Google Scholar 

  • Burckhardt I, Zimmermann S (2011) Using matrix-assisted laser desorption ionization-time of flight mass spectrometry to detect carbapenem resistance within 1 to 2.5 hours. J Clin Microbiol 49(9):3321–3324

    Article  CAS  Google Scholar 

  • Cherkaoui A, Hibbs J, Emonet S, Tangomo M, Girard M, Francois P, Schrenzel J (2010) Comparison of two matrix-assisted laser desorption ionization-time of flight mass spectrometry methods with conventional phenotypic identification for routine identification of bacteria to the species level. J Clin Microbiol 48(4):1169–1175

    Article  CAS  Google Scholar 

  • Christner M, Rohde H, Wolters M, Sobottka I, Wegscheider K, Aepfelbacher M (2010) 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(5):1584–1591

    Article  CAS  Google Scholar 

  • Claydon MA, Davey SN, Edwards-Jones V, Gordon DB (1996) The rapid identification of intact microorganisms using mass spectrometry. Nat Biotechnol 14(11):1584–1586

    Article  CAS  Google Scholar 

  • Demirev PA, Ho YP, Ryzhov V, Fenselau C (1999) Microorganism identification by mass spectrometry and protein database searches. Anal Chem 71(14):2732–2738

    Article  CAS  Google Scholar 

  • Dieckmann R, Malorny B (2011) Rapid screening of epidemiologically important Salmonella enterica subsp. enterica serovars by whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry. Appl Environ Microbiol 77(12):4136–4146

    Article  CAS  Google Scholar 

  • Dieckmann R, Helmuth R, Erhard M, Malorny B (2008) Rapid classification and identification of Salmonellae at the species and subspecies levels by whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry. Appl Environ Microbiol 74(24):7767–7778

    Article  CAS  Google Scholar 

  • Du Z, Yang R, Guo Z, Song Y, Wang J (2002) Identification of Staphylococcus aureus and determination of its methicillin resistance by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anal Chem 74(21):5487–5491

    Article  CAS  Google Scholar 

  • Eigner U, Holfelder M, Oberdorfer K, Betz-Wild U, Bertsch D, Fahr AM (2009) Performance of a matrix-assisted laser desorption ionization-time-of-flight mass spectrometry system for the identification of bacterial isolates in the clinical routine laboratory. Clin Lab 55(7–8):289–296

    CAS  Google Scholar 

  • Erhard M, Hipler UC, Burmester A, Brakhage AA, Wostemeyer J (2008) Identification of dermatophyte species causing onychomycosis and tinea pedis by MALDI-TOF mass spectrometry. Exp Dermatol 17(4):356–361

    Article  Google Scholar 

  • Espinal P, Seifert H, Dijkshoorn L, Vila J, Roca I (2011) Rapid and accurate identification of genomic species from the Acinetobacter baumannii (Ab) group by MALDI-TOF MS. Clin Microbiol Infect, 10.1111/j.1469-0691.2011.03696.x [doi]

  • Fenselau C, Demirev PA (2001) Characterization of intact microorganisms by MALDI mass spectrometry. Mass Spectrom Rev 20(4):157–171

    Article  CAS  Google Scholar 

  • Ferreira L, Sanchez-Juanes F, Gonzalez-Avila M, Cembrero-Fucinos D, Herrero-Hernandez A, Gonzalez-Buitrago JM, Munoz-Bellido JL (2010) Direct identification of urinary tract pathogens from urine samples by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 48(6):2110–2115

    Article  CAS  Google Scholar 

  • Ferreira L, Sanchez-Juanes F, Munoz-Bellido JL, Gonzalez-Buitrago JM (2011) 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(7):1007–1012

    Article  CAS  Google Scholar 

  • Ferroni A, Suarez S, Beretti JL, Dauphin B, Bille E, Meyer J, Bougnoux ME, Alanio A, Berche P, Nassif X (2010) 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(5):1542–1548

    Article  CAS  Google Scholar 

  • Friedrichs C, Rodloff AC, Chhatwal GS, Schellenberger W, Eschrich K (2007) Rapid identification of viridans streptococci by mass spectrometric discrimination. J Clin Microbiol 45(8):2392–2397

    Article  CAS  Google Scholar 

  • Grosse-Herrenthey A, Maier T, Gessler F, Schaumann R, Bohnel H, Kostrzewa M, Kruger M (2008) Challenging the problem of clostridial identification with matrix-assisted laser desorption and ionization–time-of-flight mass spectrometry (MALDI-TOF MS). Anaerobe 14(4):242–249

    Article  CAS  Google Scholar 

  • Haigh J, Degun A, Eydmann M, Millar M, Wilks M (2011) Improved performance of bacterium and yeast identification by a commercial matrix-assisted laser desorption ionization–time of flight mass spectrometry system in the clinical microbiology laboratory. J Clin Microbiol 49(9):3441

    Article  Google Scholar 

  • Hettick JM, Green BJ, Buskirk AD, Kashon ML, Slaven JE, Janotka E, Blachere FM, Schmechel D, Beezhold DH (2008a) Discrimination of Aspergillus isolates at the species and strain level by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry fingerprinting. Anal Biochem 380(2):276–281

    Article  CAS  Google Scholar 

  • Hettick JM, Green BJ, Buskirk AD, Kashon ML, Slaven JE, Janotka E, Blachere FM, Schmechel D, Beezhold DH (2008b) Discrimination of Penicillium isolates by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry fingerprinting. Rapid Commun Mass Spectrom 22(16):2555–2560

    Article  CAS  Google Scholar 

  • Hillenkamp F, Karas M (1990) Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods Enzymol 193:280–295

    Article  CAS  Google Scholar 

  • Holland RD, Wilkes JG, Rafii F, Sutherland JB, Persons CC, Voorhees KJ, Lay JO Jr (1996) Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 10(10):1227–1232

    Article  CAS  Google Scholar 

  • Holler JG, Pedersen LK, Calum H, Nielsen JB, Tvede M, Schonning K, Knudsen JD (2011) Using MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis: a case report of a patient with mitral valve infective endocarditis caused by Abiotrophia defectiva. Scand J Infect Dis 43(3):234–237

    Article  Google Scholar 

  • Hrabak J, Walkova R, Studentova V, Chudackova E, Bergerova T (2011) Carbapenemase activity detection by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 49(9):3222–3227

    Article  CAS  Google Scholar 

  • Ilina EN, Vereshchagin VA, Borovskaya AD, Malakhova MV, Sidorenko SV, Al-Khafaji NC, Kubanova AA, Govorun VM (2008) Relation between genetic markers of drug resistance and susceptibility profile of clinical Neisseria gonorrhoeae strains. Antimicrob Agents Chemother 52(6):2175–2182

    Article  CAS  Google Scholar 

  • Ilina EN, Borovskaya AD, Malakhova MM, Vereshchagin VA, Kubanova AA, Kruglov AN, Svistunova TS, Gazarian AO, Maier T, Kostrzewa M, Govorun VM (2009) Direct bacterial profiling by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry for identification of pathogenic Neisseria. J Mol Diagn 11(1):75–86

    Article  CAS  Google Scholar 

  • Ilina EN, Borovskaya AD, Serebryakova MV, Chelysheva VV, Momynaliev KT, Maier T, Kostrzewa M, Govorun VM (2010) Application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the study of Helicobacter pylori. Rapid Commun Mass Spectrom 24(3):328–334

    Article  CAS  Google Scholar 

  • Jackson KA, Edwards-Jones V, Sutton CW, Fox AJ (2005) Optimisation of intact cell MALDI method for fingerprinting of methicillin-resistant Staphylococcus aureus. J Microbiol Methods 62(3):273–284

    Article  CAS  Google Scholar 

  • Jarman KH, Cebula ST, Saenz AJ, Petersen CE, Valentine NB, Kingsley MT, Wahl KL (2000) An algorithm for automated bacterial identification using matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 72(6):1217–1223

    Article  CAS  Google Scholar 

  • Krishnamurthy T, Ross PL (1996) Rapid identification of bacteria by direct matrix-assisted laser desorption/ionization mass spectrometric analysis of whole cells. Rapid Commun Mass Spectrom 10(15):1992–1996

    Article  CAS  Google Scholar 

  • Krishnamurthy T, Ross PL, Rajamani U (1996) Detection of pathogenic and non-pathogenic bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 10(8):883–888

    Article  CAS  Google Scholar 

  • La Scola B, Raoult D (2009) Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. PLoS One 4(11):e8041

    Article  Google Scholar 

  • Lartigue MF, Hery-Arnaud G, Haguenoer E, Domelier AS, Schmit PO, van der Mee-Marquet N, Lanotte P, Mereghetti L, Kostrzewa M, Quentin R (2009) Identification of Streptococcus agalactiae Isolates from various phylogenetic lineages by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 47(7):2284–2287

    Article  Google Scholar 

  • Majcherczyk PA, McKenna T, Moreillon P, Vaudaux P (2006) The discriminatory power of MALDI-TOF mass spectrometry to differentiate between isogenic teicoplanin-susceptible and teicoplanin-resistant strains of methicillin-resistant Staphylococcus aureus. FEMS Microbiol Lett 255(2):233–239

    Article  CAS  Google Scholar 

  • Marinach-Patrice C, Lethuillier A, Marly A, Brossas JY, Gene J, Symoens F, Datry A, Guarro J, Mazier D, Hennequin C (2009) Use of mass spectrometry to identify clinical Fusarium isolates. Clin Microbiol Infect 15(7):634–642

    Article  CAS  Google Scholar 

  • Marklein G, Josten M, Klanke U, Muller E, Horre R, Maier T, Wenzel T, Kostrzewa M, Bierbaum G, Hoerauf A, Sahl HG (2009) Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and reliable identification of clinical yeast isolates. J Clin Microbiol 47(9):2912–2917

    Article  CAS  Google Scholar 

  • Martiny D, Dediste A, Debruyne L, Vlaes L, Haddou NB, Vandamme P, Vandenberg O (2011) Accuracy of the API Campy system, the Vitek 2 Neisseria-Haemophilus card and matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the identification of Campylobacter and related organisms. Clin Microbiol Infect 17(7):1001–1006

    Article  CAS  Google Scholar 

  • Marvin LF, Roberts MA, Faya LB (2003) Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in clinical chemistry. Clin Chim Acta 337(1-2):11–21

    Article  CAS  Google Scholar 

  • Mellmann A, Cloud J, Maier T, Keckevoet U, Ramminger I, Iwen P, Dunn J, Hall G, Wilson D, Lasala P, Kostrzewa M, Harmsen D (2008) Evaluation of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry in comparison to 16S rRNA gene sequencing for species identification of nonfermenting bacteria. J Clin Microbiol 46(6):1946–1954

    Article  CAS  Google Scholar 

  • Moussaoui W, Jaulhac B, Hoffmann AM, Ludes B, Kostrzewa M, Riegel P, Prevost G (2010) Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identifies 90% of bacteria directly from blood culture vials. Clin Microbiol Infect 16(11):1631–1638

    Article  CAS  Google Scholar 

  • Nagy E, Becker S, Soki J, Urban E, Kostrzewa M (2011) Differentiation of division I (cfiA-negative) and division II (cfiA-positive) Bacteroides fragilis strains by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Med Microbiol 60(Pt 11):1584–1590

    Article  CAS  Google Scholar 

  • Pignone M, Greth KM, Cooper J, Emerson D, Tang J (2006) Identification of mycobacteria by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. J Clin Microbiol 44(6):1963–1970

    Article  CAS  Google Scholar 

  • Prod’hom G, Bizzini A, Durussel C, Bille J, Greub G (2010) Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets. J Clin Microbiol 48(4):1481–1483

    Article  Google Scholar 

  • Putignani L, Del CF, Onori M, Mancinelli L, Argentieri M, Bernaschi P, Coltella L, Lucignano B, Pansani L, Ranno S, Russo C, Urbani A, Federici G, Menichella D (2011) MALDI-TOF mass spectrometry proteomic phenotyping of clinically relevant fungi. Mol Biosyst 7(3):620–629

    Article  CAS  Google Scholar 

  • Sauer S, Freiwald A, Maier T, Kube M, Reinhardt R, Kostrzewa M, Geider K (2008) Classification and identification of bacteria by mass spectrometry and computational analysis. PLoS ONE 3(7):e2843

    Article  Google Scholar 

  • Schubert S, Weinert K, Wagner C, Gunzl B, Wieser A, Maier T, Kostrzewa M (2011) novel, improved sample preparation for rapid, direct identification from positive blood cultures using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. J Mol Diagn 13(6):701–706

    Article  CAS  Google Scholar 

  • Seibold E, Maier T, Kostrzewa M, Zeman E, Splettstoesser W (2010) Identification of Francisella tularensis by whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry: fast, reliable, robust, and cost-effective differentiation on species and subspecies levels. J Clin Microbiol 48(4):1061–1069

    Article  CAS  Google Scholar 

  • Seng P, Drancourt M, Gouriet F, La SB, Fournier PE, Rolain JM, Raoult D (2009) Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin Infect Dis 49(4):543–551

    Article  CAS  Google Scholar 

  • Sparbier K, Schubert S, Weller U, Boogen C, Kostrzewa M (2012) MALDI-TOF MS based functional assay for the rapid detection of resistance against ß-lactam antibiotics. J Clin Micro (in press)

  • Stephan R, Cernela N, Ziegler D, Pfluger V, Tonolla M, Ravasi D, Fredriksson-Ahomaa M, Hachler H (2011) Rapid species specific identification and subtyping of Yersinia enterocolitica by MALDI-TOF mass spectrometry. J Microbiol Methods 87(2):150–153

    Article  CAS  Google Scholar 

  • Stevenson LG, Drake SK, Murray PR (2010) Rapid identification of bacteria in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 48(2):444–447

    Article  CAS  Google Scholar 

  • van Veen SQ, Claas EC, Kuijper EJ (2010) High-throughput identification of bacteria and yeast by matrix-assisted laser desorption ionization-time of flight mass spectrometry in conventional medical microbiology laboratories. J Clin Microbiol 48(3):900–907

    Article  Google Scholar 

  • Vanlaere E, Sergeant K, Dawyndt P, Kallow W, Erhard M, Sutton H, Dare D, Devreese B, Samyn B, Vandamme P (2008) Matrix-assisted laser desorption ionisation-time-of of-flight mass spectrometry of intact cells allows rapid identification of Burkholderia cepacia complex. J Microbiol Methods 75(2):279–286

    Article  CAS  Google Scholar 

  • Wolters M, Rohde H, Maier T, Belmar-Campos C, Franke G, Scherpe S, Aepfelbacher M, Christner M (2011) MALDI-TOF MS fingerprinting allows for discrimination of major methicillin-resistant Staphylococcus aureus lineages. Int J Med Microbiol 301(1):64–68

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work to refine the diagnostic MALDI-TOF MS technology in our lab was supported by Bayerische Forschungsstiftung (FORPROTECT—Protection against infectious diseases, new diagnostic, and therapeutic approaches).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sören Schubert.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wieser, A., Schneider, L., Jung, J. et al. MALDI-TOF MS in microbiological diagnostics—identification of microorganisms and beyond (mini review). Appl Microbiol Biotechnol 93, 965–974 (2012). https://doi.org/10.1007/s00253-011-3783-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-011-3783-4

Keywords

Navigation