Applied Microbiology and Biotechnology

, Volume 99, Issue 11, pp 4595–4614 | Cite as

Biomarkers for infection: enzymes, microbes, and metabolites

  • Gregor Tegl
  • Doris SchifferEmail author
  • Eva Sigl
  • Andrea Heinzle
  • Georg M. Guebitz


Wound infection is a severe complication causing delayed healing and risks for patients. Conventional methods of diagnosis for infection involve error-prone clinical description of the wound and time-consuming microbiological tests. More reliable alternatives are still rare, except for invasive and unaffordable gold standard methods. This review discusses the diversity of new approaches for wound infection determination. There has been progress in the detection methods of microorganisms, including the assessment of the diversity of the bacterial community present in a wound, as well as in the elaboration of specific markers. Another interesting strategy involves the quantification of enzyme activities in the wound fluid secreted by the immune system as response to infection. Color-changing substrates for these enzymes consequently have been shown to allow detection of an infection in wounds in a fast and easy way. Promising results were also delivered in measuring pH changes or detecting enhanced amounts of volatile molecules in case of infection. A simple and effective infection detection tool is not yet on the market, but innovative ideas pave the way for the investigation of fast and easy point-of-care devices.


Infection detection Chronic wounds Sensors Diagnostic Point of care 



This work was supported by the Federal Ministry of Science, Research and Economy (BMWFW), the Federal Ministry of Traffic, Innovation and Technology (bmvit), the Styrian Business Promotion Agency SFG, the Standortagentur Tirol, and ZIT—Technology Agency of the City of Vienna through the COMET-Funding Program managed by the Austrian Research Promotion Agency FFG. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 604278

Conflict of interest



  1. Abbott RE, Corral CJ, MacIvor DM, Lin X, Ley TJ, Mustoe TA (1998) Augmented inflammatory responses and altered wound healing in cathepsin G-deficient mice. Arch Surg 133:1002–1006. doi: 10.1001/archsurg.133.9.1002 PubMedGoogle Scholar
  2. Agrawal S, Prajapati R (2012) Nanosensors and their pharmaceutical applications: a review. Int J Pharm Sci Nanotechnol 4:1528–1536Google Scholar
  3. Ågren MS, Mirastschijski U, Karlsmark TS-KU (2001) Topical synthetic inhibitor of matrix metalloproteinases delays epidermal regeneration of human wounds. Exp Dermatol 10:337–348PubMedGoogle Scholar
  4. Bailey A, Pisanelli AM, Persaud KC (2008) Development of conducting polymer sensor arrays for wound monitoring. Sensors Actuators B Chem 131:5–9. doi: 10.1016/j.snb.2007.12.035 Google Scholar
  5. Be N, Allen JE, Brown TS, Gardner SN, McLoughlin KS, Forsberg JA, Kirkup BC, Chromy B, Luciw P, Elster E, Jaing CJ (2014) Microbial profiling of combat wound infection through detection microarray and next-generation sequencing. J Clin Microbiol 52:2583–2594. doi: 10.1128/JCM.00556-14 PubMedCentralPubMedGoogle Scholar
  6. Biswas S, Rolain JM (2013) Use of MALDI-TOF mass spectrometry for identification of bacteria that are difficult to culture. J Microbiol Methods 92:14–24. doi: 10.1016/j.mimet.2012.10.014 PubMedGoogle Scholar
  7. Bopp AF, Goynes W (2005) Detection of human neutrophil elastase with ethoxylate acrylate resin analogs. J Pept Res 66:160–168PubMedGoogle Scholar
  8. Brocklesby KL, Johns SC, Jones AE, Sharp D, Smith RB (2013) Smart bandages–a colourful approach to early stage infection detection and control in wound care. Med Hypotheses 80:237–240. doi: 10.1016/j.mehy.2012.11.037 PubMedGoogle Scholar
  9. Broszczak D, Stupar D, All C, Mvs S, Tj P, Gk S, Upton Z (2012) Biochemical profiling of proteins and metabolites in wound exudate from chronic wound environments. Wound Pract Res 20:62–72Google Scholar
  10. Caliendo AM, Gilbert DN, Ginocchio CC, Hanson KE, May L, Quinn TC, Tenover FC, Alland D, Blaschke AJ, Bonomo RA, Carroll KC, Ferraro MJ, Hirschhorn LR, Joseph WP, Karchmer T, MacIntyre AT, Reller LB, Jackson AF (2013) Better tests, better care: improved diagnostics for infectious diseases. Clin Infect Dis 57(Suppl 3):S139–S170. doi: 10.1093/cid/cit578 PubMedCentralPubMedGoogle Scholar
  11. Carlsson J (1973) Simplified gas chromatographic procedure for identification of bacterial metabolic products. Appl Microbiol 25:287–289PubMedCentralPubMedGoogle Scholar
  12. Chen C, Zhao J, Jiang J, Yu R (2012) A novel exonuclease III-aided amplification assay for lysozyme based on graphene oxide platform. Talanta 101:357–361. doi: 10.1016/j.talanta.2012.09.041 PubMedGoogle Scholar
  13. Chowdhury F, Chowdhury A (2009) Pyrosequencing-an alternative to traditional Sanger sequencing. Am J Biochem Biotechnol 8:14–20Google Scholar
  14. Ciani I, Schulze H, Corrigan DK, Henihan G, Giraud G, Terry JG, Walton AJ, Pethig R, Ghazal P, Crain J, Campbell CJ, Bachmann TT, Mount AR (2012) Development of immunosensors for direct detection of three wound infection biomarkers at point of care using electrochemical impedance spectroscopy. Biosens Bioelectron 31:413–418. doi: 10.1016/j.bios.2011.11.004 PubMedGoogle Scholar
  15. Cutting KF, White RJ (2005) Criteria for identifying wound infection–revisited. Ostomy Wound Manag 51:28–34Google Scholar
  16. Dale DC, Boxer L, Liles WC (2008) The phagocytes: neutrophils and monocytes. Blood 112:935–945. doi: 10.1182/blood-2007-12-077917 PubMedGoogle Scholar
  17. Dargaville TR, Farrugia BL, Broadbent JA, Pace S, Upton Z, Voelcker NH (2013) Sensors and imaging for wound healing: a review. Biosens Bioelectron 41:30–42. doi: 10.1016/j.bios.2012.09.029 PubMedGoogle Scholar
  18. Davies CE, Hill KE, Wilson MJ, Stephens P, Hill CM, Harding KG, Thomas DW (2004) Use of 16S ribosomal DNA PCR and denaturing gradient gel electrophoresis for analysis of the microfloras of healing and nonhealing chronic venous leg ulcers. J Clin Microbiol 42:3549–3557. doi: 10.1128/JCM.42.8.3549-3557.2004 PubMedCentralPubMedGoogle Scholar
  19. Davies CE, Hill KE, Newcombe RG, Stephens P, Wilson MJ, Harding KG, Thomas DW (2006) A prospective study of the microbiology of chronic venous leg ulcers to reevaluate the clinical predictive value of tissue biopsies and swabs. Wound Repair Regen 15:17–22. doi: 10.1111/j.1524-475X.2006.00180.x Google Scholar
  20. De Bruyne K, Slabbinck B, Waegeman W, Vauterin P, De Baets B, Vandamme P (2011) Bacterial species identification from MALDI-TOF mass spectra through data analysis and machine learning. Syst Appl Microbiol 34:20–29. doi: 10.1016/j.syapm.2010.11.003 PubMedGoogle Scholar
  21. Drinkwater SL, Smith A, Burnand KG (2002) What can wound fluids tell us about the venous ulcer microenvironment? Int J Low Extrem Wounds 1:184–190. doi: 10.1177/153473460200100307 PubMedGoogle Scholar
  22. Du Clos TW (2000) Function of C-reactive protein. Ann Med 32:274–278PubMedGoogle Scholar
  23. Erdem A, Eksin E, Muti M (2014) Chitosan-graphene oxide based aptasensor for the impedimetric detection of lysozyme. Colloids Surf B: Biointerfaces 115:205–211. doi: 10.1016/j.colsurfb.2013.11.037 PubMedGoogle Scholar
  24. Feng J, Tian F, Yan J, He Q, Shen Y, Pan L (2011) A background elimination method based on wavelet transform in wound infection detection by electronic nose. Sensors Actuators B Chem 157:395–400. doi: 10.1016/j.snb.2011.04.069 Google Scholar
  25. Feng J, Tian F, Jia P, He Q, Shen Y, Liu T (2013) Feature selection using support vector machines and independent component analysis for wound infection detection by electronic nose. Sensors Mater 25:527–538Google Scholar
  26. Fernandez ML, Upton Z, Edwards H, Finlayson K, Shooter GK (2012) Elevated uric acid correlates with wound severity. Int Wound J 9:139–149. doi: 10.1111/j.1742-481X.2011.00870.x PubMedGoogle Scholar
  27. Fleming A (1922) On a remarkable bacteriolytic element found in tissues and secretions. Proc R Soc B 93:306–317Google Scholar
  28. Franck T, Kohnen S, Boudjeltia KZ, Van Antwerpen P, Bosseloir A, Niesten A, Gach O, Nys M, Deby-Dupont G, Serteyn D (2009) A new easy method for specific measurement of active myeloperoxidase in human biological fluids and tissue extracts. Talanta 80:723–729. doi: 10.1016/j.talanta.2009.07.052 PubMedGoogle Scholar
  29. Gao L, Mbonu N, Cao L, Gao D (2008) Label-free colorimetric detection of gelatinases on nanoporous silicon photonic films. Anal Chem 80:1468–1473. doi: 10.1021/ac701870y PubMedGoogle Scholar
  30. Gardner SE, Frantz RA, Doebbeling BN (2001) The validity of the clinical signs and symptoms used to identify localized chronic wound infection. Wound Repair Regen 9:178–186PubMedGoogle Scholar
  31. Gardner SE, Frantz RA, Saltzman CL, Hillis SL, Park H, Scherubel M (2006) Diagnostic validity of three swab techniques for identifying chronic wound infection. Wound Repair Regen 14:548–557. doi: 10.1111/j.1743-6109.2006.00162.x PubMedGoogle Scholar
  32. Gardner SE, Hillis Stephen L, Frantz R (2010) Clinical signs of infection in diabetic foot ulcers with high microbial load. Biol Res Nurs 11:119–128. doi: 10.1177/1099800408326169.Clinical Google Scholar
  33. Gethin G (2012) Understanding the inflammatory process in wound healing. Br J Community Nurs Suppl:S17–8, S20–S22.Google Scholar
  34. Gharizadeh B, Käller M, Nyrén P, Andersson A, Uhlén M, Lundeberg J, Ahmadian A (2003) Viral and microbial genotyping by a combination of multiplex competitive hybridization and specific extension followed by hybridization to generic tag arrays. Nucleic Acids Res 31, e146. doi: 10.1093/nar/gng147 PubMedCentralPubMedGoogle Scholar
  35. Gorodkiewicz E, Sieńczyk M, Regulska E, Grzywa R, Pietrusewicz E, Lesner A, Lukaszewski Z (2012) Surface plasmon resonance imaging biosensor for cathepsin G based on a potent inhibitor: development and applications. Anal Biochem 423:218–223. doi: 10.1016/j.ab.2012.01.033 PubMedGoogle Scholar
  36. Grabbe Stephan DJSLKA (2007) Influence of pH on wound-healing: a new perspective for wound-therapy? Arch Dermatol Res 298:413–420PubMedGoogle Scholar
  37. Gray E, Thomas TL, Betmouni S, Scolding N, Love S (2008) Elevated myeloperoxidase activity in white matter in multiple sclerosis. Neurosci Lett 444:195–198. doi: 10.1016/j.neulet.2008.08.035 PubMedGoogle Scholar
  38. Grzywa R, Gorodkiewicz E, Burchacka E, Lesner A, Laudański P, Lukaszewski Z, Sieńczyk M (2014) Determination of cathepsin G in endometrial tissue using a surface plasmon resonance imaging biosensor with tailored phosphonic inhibitor. Eur J Obstet Gynecol Reprod Biol 182C:38–42. doi: 10.1016/j.ejogrb.2014.08.029 Google Scholar
  39. Hajnsek M, Schiffer D, Harrich D, Koller D, Verient V, Palen JVD, Heinzle A, Binder B, Sigl E, Sinner F, Guebitz GM (2015) An electrochemical sensor for fast detection of wound infection based on myeloperoxidase activity. Sensors Actuators B Chem 209:265–274. doi: 10.1016/j.snb.2014.11.125 Google Scholar
  40. Hamid M (2009) Potential applications of peroxidases. Food Chem 115:1177–1186. doi: 10.1016/j.foodchem.2009.02.035 Google Scholar
  41. Hansson M, Olsson I, Nauseef WM (2006) Biosynthesis, processing, and sorting of human myeloperoxidase. Arch Biochem Biophys 445:214–224. doi: 10.1016/ PubMedGoogle Scholar
  42. Haqqani AS, Sandhu JK, Birnboim HC (1999) A myeloperoxidase-specific assay based upon bromide-dependent chemiluminescence of luminol. Anal Biochem 273:126–132. doi: 10.1006/abio.1999.4206 PubMedGoogle Scholar
  43. Hardt M, Guo Y, Henderson G, Laine RA (2003) Zymogram with Remazol brilliant blue-labeled Micrococcus lysodeikticus cells for the detection of lysozymes: example of a new lysozyme activity in Formosan termite defense secretions. Anal Biochem 312:73–76. doi: 10.1016/S0003-2697(02)00443-8 PubMedGoogle Scholar
  44. Harrison R (2002) Structure and function of xanthine oxidoreductase: where are we now? Free Radic Biol Med 33:774–797PubMedGoogle Scholar
  45. Hasmann A, Gewessler U, Hulla E, Schneider KP, Binder B, Francesko A, Tzanov T, Schintler M, Van der Palen J, Guebitz GM, Wehrschuetz-Sigl E (2011a) Sensor materials for the detection of human neutrophil elastase and cathepsin G activity in wound fluid. Exp Dermatol 20:508–513. doi: 10.1111/j.1600-0625.2011.01256.x PubMedGoogle Scholar
  46. Hasmann A, Wehrschuetz-Sigl E, Kanzler G, Gewessler U, Hulla E, Schneider KP, Binder B, Schintler M, Guebitz GM (2011b) Novel peptidoglycan-based diagnostic devices for detection of wound infection. Diagn Microbiol Infect Dis 71:12–23. doi: 10.1016/j.diagmicrobio.2010.09.009 PubMedGoogle Scholar
  47. Hasmann A, Wehrschuetz-Sigl E, Marold A, Wiesbauer H, Schoeftner R, Gewessler U, Kandelbauer A, Schiffer D, Schneider KP, Binder B, Schintler M, Guebitz GM (2013) Analysis of myeloperoxidase activity in wound fluids as a marker of infection. Ann Clin Biochem 50:245–254PubMedGoogle Scholar
  48. He J-L, Wu Z-S, Zhang S-B, Shen G-L, Yu R-Q (2010) Fluorescence aptasensor based on competitive-binding for human neutrophil elastase detection. Talanta 80:1264–1268. doi: 10.1016/j.talanta.2009.09.019 PubMedGoogle Scholar
  49. He Q, Yan J, Shen Y, Bi Y, Ye G, Tian F, Wang Z (2012) Classification of electronic nose data in wound infection detection based on PSO-SVM combined with wavelet transform. Intell Autom Soft Comput 18:967–979. doi: 10.1080/10798587.2012.10643302 Google Scholar
  50. Heinzle A, Papen-Botterhuis NE, Schiffer D, Schneider KP, Binder B, Schintler M, Haaksman IK, Lenting HB, Gübitz GM, Sigl E (2013) Novel protease-based diagnostic devices for detection of wound infection. Wound Repair Regen 21:482–489. doi: 10.1111/wrr.12040 PubMedGoogle Scholar
  51. Herrasti Z, Martínez F, Baldrich E (2014) Carbon nanotube wiring for signal amplification of electrochemical magneto immunosensors: application to myeloperoxidase detection. Anal Bioanal Chem 406:5487–5493. doi: 10.1007/s00216-014-7954-x PubMedGoogle Scholar
  52. Holland LA, Chetwyn NP, Perkins MD, Lunte SM (1997) Capillary electrophoresis in pharmaceutical analysis. Pharm Res 14:372–387PubMedGoogle Scholar
  53. Howell-Jones RS, Wilson MJ, Hill KE, Howard AJ, Price PE, Thomas DW (2005) A review of the microbiology, antibiotic usage and resistance in chronic skin wounds. J Antimicrob Chemother 55:143–149. doi: 10.1093/jac/dkh513 PubMedGoogle Scholar
  54. Jia P, Tian F, He Q, Fan S, Liu J, Yang SX (2014) Feature extraction of wound infection data for electronic nose based on a novel weighted KPCA. Sensors Actuators B Chem 201:555–566. doi: 10.1016/j.snb.2014.05.025 Google Scholar
  55. Jiang Z-L, Huang G-X (2007) Resonance scattering spectra of Micrococcus lysodeikticus and its application to assay of lysozyme activity. Clin Chim Acta 376:136–141. doi: 10.1016/j.cca.2006.08.005 PubMedGoogle Scholar
  56. Klebanoff SJ (2005) Myeloperoxidase: friend and foe. J Leukoc Biol 77:598–625. doi: 10.1189/jlb.1204697.1 PubMedGoogle Scholar
  57. Laschtschenko P (1909) Uber die keimtötende und entwicklungshemmende Wirkung von Hühnereiweiß. Zeitschrift für Hyg und Infekt 64:419–427Google Scholar
  58. Lau D, Baldus S (2006) Myeloperoxidase and its contributory role in inflammatory vascular disease. Pharmacol Ther 111:16–26. doi: 10.1016/j.pharmthera.2005.06.023 PubMedGoogle Scholar
  59. Li L-D, Chen Z-B, Zhao H-T, Guo L, Mu X (2010) An aptamer-based biosensor for the detection of lysozyme with gold nanoparticles amplification. Sensors Actuators B Chem 149:110–115. doi: 10.1016/j.snb.2010.06.015 Google Scholar
  60. Lian Y, He F, Mi X, Tong F, Shi X (2014) Lysozyme aptamer biosensor based on electron transfer from SWCNTs to SPQC-IDE. Sensors Actuators B Chem 199:377–383. doi: 10.1016/j.snb.2014.04.001 Google Scholar
  61. Lipsky BA (2012) Expert opinion on the management of infections in the diabetic foot. Diabetes Metab Res Rev 28:163–178. doi: 10.1002/dmrr PubMedGoogle Scholar
  62. Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, LeFrock JL, Lew DP, Mader JT, Norden C, Tan JS (2004) Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 39:885–910. doi: 10.1086/424846 PubMedGoogle Scholar
  63. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJG, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E, Infectious Diseases Society of America (2012) 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 54:e132–e173. doi: 10.1093/cid/cis346 PubMedGoogle Scholar
  64. Liu B, Lu L, Li Q, Xie G (2011) Disposable electrochemical immunosensor for myeloperoxidase based on the indium tin oxide electrode modified with an ionic liquid composite film containing gold nanoparticles, poly(o-phenylenediamine) and carbon nanotubes. Microchim Acta 173:513–520. doi: 10.1007/s00604-011-0575-6 Google Scholar
  65. Lu L, Liu B, Liu C, Xie G (2010) Amperometric immunosensor for myeloperoxidase in human serum based on a multi-wall carbon nanotubes-ionic liquid-cerium dioxide film-modified electrode. Bull Korean Chem Soc 31:3259–3264. doi: 10.5012/bkcs.2010.31.11.3259 Google Scholar
  66. Malic S, Hill KE, Hayes A, Percival SL, Thomas DW, Williams DW (2009) Detection and identification of specific bacteria in wound biofilms using peptide nucleic acid fluorescent in situ hybridization (PNA FISH). Microbiology 155:2603–2611. doi: 10.1099/mic.0.028712-0 PubMedGoogle Scholar
  67. Mark E, Rupp, Paul D, Fey (2003) Extended spectrum β-Lactamase (ESBL)-producing Enterobacteriaceae consideration for diagnosis, prevention and drug treatment. Drugs 63:353–365Google Scholar
  68. Martin M, Taleb Bendiab C, Massif L, Palestino G, Agarwal V, Cuisinier F, Gergely C (2011) Matrix metalloproteinase sensing via porous silicon microcavity devices functionalized with human antibodies. Phys Status Solidi 8:1888–1892. doi: 10.1002/pssc.201000155 Google Scholar
  69. Mazumdar RM, Chowdhury A, Hossain N, Mahajan S, Islam S (2013) Pyrosequencing-a next generation sequencing technology. World Appl Sci J 24(24):1558–1571. doi: 10.5829/idosi.wasj.2013.24.12.2972 Google Scholar
  70. McDonnell B, Hearty S, Finlay WJJ, O’Kennedy R (2011) A high-affinity recombinant antibody permits rapid and sensitive direct detection of myeloperoxidase. Anal Biochem 410:1–6. doi: 10.1016/j.ab.2010.09.039 PubMedGoogle Scholar
  71. Melendez JH, Frankel YM, An AT, Williams L, Price LB, Wang N-Y, Lazarus GS, Zenilman JM (2010) Real-time PCR assays compared to culture-based approaches for identification of aerobic bacteria in chronic wounds. Clin Microbiol Infect 16:1762–1769. doi: 10.1111/j.1469-0691.2010.03158.x PubMedGoogle Scholar
  72. Moore WGI, Bodden MK, Windsor LJ, Decarlo A, Engler JA (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4:197–250PubMedGoogle Scholar
  73. Neumaier M, Scherer M (2008) C-reactive protein levels for early detection of postoperative infection after fracture surgery in 787 patients. Acta Orthop 79:428–432. doi: 10.1080/17453670710015355 PubMedGoogle Scholar
  74. Persaud KC (2005) Medical applications of odor-sensing devices. Int J Low Extrem Wounds 4:50–56. doi: 10.1177/1534734605275139 PubMedGoogle Scholar
  75. Phair J, Newton L, McCormac C, Cardosi MF, Leslie R, Davis J (2011) A disposable sensor for point of care wound pH monitoring. Analyst 136:4692–4695. doi: 10.1039/c1an15675f PubMedGoogle Scholar
  76. Price LB, Liu CM, Melendez JH, Frankel YM, Engelthaler D, Aziz M, Bowers J, Rattray R, Ravel J, Kingsley C, Keim PS, Lazarus GS, Zenilman JM (2009) Community analysis of chronic wound bacteria using 16S rRNA gene-based pyrosequencing: impact of diabetes and antibiotics on chronic wound microbiota. PLoS One 4, e6462. doi: 10.1371/journal.pone.0006462 PubMedCentralPubMedGoogle Scholar
  77. Puchberger-Enengl D, Krutzler C, Vellekoop MJ, Gusshausstrasse E (2011) Organically modified silicate film pH sensor for continuous wound monitoring. Sensors, IEEE. 679–682Google Scholar
  78. Pulli B, Ali M, Forghani R, Schob S, Hsieh KLC, Wojtkiewicz G, Linnoila JJ, Chen JW (2013) Measuring myeloperoxidase activity in biological samples. PLoS One 8, e67976. doi: 10.1371/journal.pone.0067976 PubMedCentralPubMedGoogle Scholar
  79. Reynolds WF, Rhees J, Maciejewski D, Paladino T, Sieburg H, Maki RA, Masliah E (1999) Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer’s disease. Exp Neurol 155:31–41. doi: 10.1006/exnr.1998.6977 PubMedGoogle Scholar
  80. Richard J-L, Sotto A, Lavigne J-P (2011) New insights in diabetic foot infection. World J Diabetes 2:24–32. doi: 10.4239/wjd.v2.i2.24 PubMedCentralPubMedGoogle Scholar
  81. Rodríguez MC, Rivas GA (2009) Label-free electrochemical aptasensor for the detection of lysozyme. Talanta 78:212–216. doi: 10.1016/j.talanta.2008.11.002 PubMedGoogle Scholar
  82. Rudolph V, Andrié RP, Rudolph TK, Friedrichs K, Klinke A, Hirsch-Hoffmann B, Schwoerer AP, Lau D, Fu X, Klingel K, Sydow K, Didié M, Seniuk A, von Leitner E-C, Szoecs K, Schrickel JW, Treede H, Wenzel U, Lewalter T, Nickenig G, Zimmermann W-H, Meinertz T, Böger RH, Reichenspurner H, Freeman BA, Eschenhagen T, Ehmke H, Hazen SL, Willems S, Baldus S (2010) Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation. Nat Med 16:470–474. doi: 10.1038/nm.2124 PubMedCentralPubMedGoogle Scholar
  83. Salman M (2013) A novel multiplex PCR for detection of Pseudomonas aeruginosa: a major cause of wound infections. Pakistan J Med Sci 29:957–961. doi: 10.12669/pjms.294.3652 Google Scholar
  84. Schiffer D, Verient V, Luschnig D, Blokhuis-Arkes MHE, Palen JVD, Gamerith C, Burnet M, Sigl E, Heinzle A, Guebitz GM (2015) Lysozyme-responsive polymer systems for detection of infection. Eng Life Sci. doi: 10.1002/elsc.201400145 Google Scholar
  85. Schneider KP, Gewessler U, Flock T, Heinzle A, Schenk V, Kaufmann F, Sigl E, Guebitz GM (2012) Signal enhancement in polysaccharide based sensors for infections by incorporation of chemically modified laccase. N Biotechnol 29:502–509. doi: 10.1016/j.nbt.2012.03.005 PubMedGoogle Scholar
  86. Schreml S, Meier R (2011) 2D luminescence imaging of pH in vivo. Proc Natl Acad Sci 108:2432–2437. doi: 10.1073/pnas.1006945108/-/ PubMedCentralPubMedGoogle Scholar
  87. Schreml S, Meier RJ, Wolfbeis OS, Landthaler M, Szeimies R (2010) 2D luminescence imaging of pH in vivo. PNAS. doi: 10.1073/pnas.1006945108/-/ Google Scholar
  88. Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT (2009) Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen 17:763–771. doi: 10.1111/j.1524-475X.2009.00543.x.Human PubMedCentralPubMedGoogle Scholar
  89. Sener G, Ozgur E, Yılmaz E, Uzun L, Say R, Denizli A (2010) Quartz crystal microbalance based nanosensor for lysozyme detection with lysozyme imprinted nanoparticles. Biosens Bioelectron 26:815–821. doi: 10.1016/j.bios.2010.06.003 PubMedGoogle Scholar
  90. Šetkus A, Galdikas A-J, Kancleris Ž-A, Olekas A, Senulienė D, Strazdienė V, Rimdeika R, Bagdonas R (2006) Featuring of bacterial contamination of wounds by dynamic response of SnO2 gas sensor array. Sensors Actuators B Chem 115:412–420. doi: 10.1016/j.snb.2005.10.003 Google Scholar
  91. Sharp D (2013) Printed composite electrodes for in-situ wound pH monitoring. Biosens Bioelectron 50:399–405. doi: 10.1016/j.bios.2013.06.042 PubMedGoogle Scholar
  92. Sharp D, Davis J (2008) Integrated urate sensors for detecting wound infection. Electrochem Commun 10:709–713. doi: 10.1016/j.elecom.2008.02.025 Google Scholar
  93. Sharp D, Gladstone P, Smith RB, Forsythe S, Davis J (2010) Approaching intelligent infection diagnostics: carbon fibre sensor for electrochemical pyocyanin detection. Bioelectrochemistry 77:114–119. doi: 10.1016/j.bioelechem.2009.07.008 PubMedGoogle Scholar
  94. Sibley CD, Peirano G, Church DL (2012) Molecular methods for pathogen and microbial community detection and characterization: current and potential application in diagnostic microbiology. Infect Genet Evol 12:505–521PubMedGoogle Scholar
  95. Siddiqui AR, Bernstein JM (2010) Chronic wound infection: facts and controversies. Clin Dermatol 28:519–526. doi: 10.1016/j.clindermatol.2010.03.009 PubMedGoogle Scholar
  96. Snydman DR, Jacobus NV, McDermott LA, Supran S, Cuchural GJ, Finegold S, Harrell L, Hecht DW, Iannini P, Jenkins S, Pierson C, Rihs J, Gorbach SL (1999) Multicenter study of in vitro susceptibility of the Bacteroides fragilis group, 1995 to 1996, with comparison of resistance trends from 1990 to 1996. Antimicrob Agents Chemother 43:2417–2422PubMedCentralPubMedGoogle Scholar
  97. Song Y, Li Y, Liu Z, Liu L, Wang X, Su X, Ma Q (2014) A novel ultrasensitive carboxymethyl chitosan-quantum dot-based fluorescence “turn on-off” nanosensor for lysozyme detection. Biosens Bioelectron 61:9–13. doi: 10.1016/j.bios.2014.04.036 PubMedGoogle Scholar
  98. Stair JL, Watkinson M, Krause S (2009) Sensor materials for the detection of proteases. Biosens Bioelectron 24:2113–2118. doi: 10.1016/j.bios.2008.11.002 PubMedGoogle Scholar
  99. Swirski FK, Wildgruber M, Ueno T, Figueiredo J-L, Panizzi P, Iwamoto Y, Zhang E, Stone JR, Rodriguez E, Chen JW, Pittet MJ, Weissleder R, Nahrendorf M (2010) Myeloperoxidase-rich Ly-6C+ myeloid cells infiltrate allografts and contribute to an imaging signature of organ rejection in mice. J Clin Invest 120:2627–2634. doi: 10.1172/JCI42304 PubMedCentralPubMedGoogle Scholar
  100. Szeliga J, Ewa Kłodzińska MJ (2011) The clinical use of a fast screening test based on technology of capillary zone electrophoresis (CZE) for identification of Escherichia coli infection in biological material. Med Sci Monit 17:91–96Google Scholar
  101. Tong J, Liu C, Summanen P, Xu H, Finegold SM (2011) Application of quantitative real-time PCR for rapid identification of Bacteroides fragilis group and related organisms in human wound samples. Anaerobe 17:64–68. doi: 10.1016/j.anaerobe.2011.03.004 PubMedGoogle Scholar
  102. Torsteinsdóttir I, Hâkansson L, Hällgren R, Gudbjörnsson B, Arvidson NG, Venge P (1999) Serum lysozyme: a potential marker of monocyte/macrophage activity in rheumatoid arthritis. Rheumatology (Oxford) 38:1249–1254. doi: 10.1093/rheumatology/38.12.1249 Google Scholar
  103. Van Delden C, Iglewski BH (1998) Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg Infect Dis 4:551–560. doi: 10.3201/eid0404.980405 PubMedCentralPubMedGoogle Scholar
  104. Williams DT, Hilton JR, Harding KG (2004) Diagnosing foot infection in diabetes. Clin Infect Dis 39:S83–S86. doi: 10.1086/383267 PubMedGoogle Scholar
  105. Windmiller JR, Chinnapareddy S, Santhosh P, Halámek J, Chuang MC, Bocharova V, Tseng TF, Chou TY, Katz E, Wang J (2010) Strip-based amperometric detection of myeloperoxidase. Biosens Bioelectron 26:886–889. doi: 10.1016/j.bios.2010.07.031 PubMedGoogle Scholar
  106. Wu YC, Kulbatski I, Medeiros PJ, Maeda A, Bu J, Xu L, Chen Y, DaCosta RS (2014) Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies. J Biomed Opt 19:085002. doi: 10.1117/1.JBO.19.8.085002 PubMedGoogle Scholar
  107. Yager DR, Kulina RA, Gilman LA (2007) Wound fluids: a window into the wound environment? Int J Low Extrem Wounds 6:262–272. doi: 10.1177/1534734607307035 PubMedGoogle Scholar
  108. Yan J, Tian F, He Q, Shen Y (2012) Feature extraction from sensor data for detection of wound pathogen based on electronic nose. Sensors Mater 24:57–73Google Scholar
  109. Yoshida W, Abe K, Ikebukuro K (2014) Emerging techniques employed in aptamer-based diagnostic tests. Expert Rev Mol Diagn 14:143–151. doi: 10.1586/14737159.2014.868307 PubMedGoogle Scholar
  110. Zhou J, Loftus AL, Mulley G, Jenkins ATA (2010) A thin film detection/response system for pathogenic bacteria. J Am Chem Soc 132:6566–6570. doi: 10.1021/ja101554a PubMedGoogle Scholar
  111. Zhou J, Tun TN, Hong S, Mercer-Chalmers JD, Laabei M, Young AER, Jenkins ATA (2011) Development of a prototype wound dressing technology which can detect and report colonization by pathogenic bacteria. Biosens Bioelectron 30:67–72. doi: 10.1016/j.bios.2011.08.028 PubMedGoogle Scholar
  112. Zou F, Schmon M, Sienczyk M, Grzywa R, Palesch D, Boehm BO, Sun ZL, Watts C, Schirmbeck R, Burster T (2012) Application of a novel highly sensitive activity-based probe for detection of cathepsin G. Anal Biochem 421:667–672. doi: 10.1016/j.ab.2011.11.016 PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Gregor Tegl
    • 1
  • Doris Schiffer
    • 1
    • 2
    Email author
  • Eva Sigl
    • 3
  • Andrea Heinzle
    • 2
    • 3
  • Georg M. Guebitz
    • 1
    • 2
  1. 1.Department of Environmental BiotechnologyUniversity of Natural Resources and Life Sciences ViennaTulln an der DonauAustria
  2. 2.Austrian Centre of Industrial BiotechnologyGrazAustria
  3. 3.Qualizyme GmbHGrazAustria

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