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Article

Functional protease profiling for laboratory based diagnosis of invasive aspergillosis

  • Authors:
    • Bassel Sabbagh
    • Victor Costina
    • Dieter Buchheidt
    • Mark Reinwald
    • Michael Neumaier
    • Peter Findeisen
  • View Affiliations / Copyright

    Affiliations: Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, University Hospital Mannheim, D-68167 Mannheim, Germany, Department of Haematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, University Hospital Mannheim, D-68167 Mannheim, Germany
  • Pages: 143-150
    |
    Published online on: May 4, 2015
       https://doi.org/10.3892/ijo.2015.2984
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Abstract

Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised patients, because diagnostic criteria according to EORTC/MSG guidelines are often not met and have low sensitivity. Hence there is an urgent need to improve diagnostic procedures by developing novel approaches. In the present study, we present a proof of concept experiment for the monitoring of Aspergillus associated protease activity in serum specimens for diagnostic purpose. Synthetic peptides that are selectively cleaved by proteases secreted from Aspergillus species were selected from our own experiments and published data. These so called reporter peptides (RP, n=5) were added to serum specimens from healthy controls (HC, n=101) and patients with proven (IA, n=9) and possible (PIA, n=144) invasive aspergillosis. Spiked samples were incubated ex vivo under strictly standardized conditions. Proteolytic fragments were analyzed using MALDI-TOF mass spectrometry. Spiked specimens of IA patients had highest concentrations of RP-fragments followed by PIA and HC. The median signal intensity was 116.546 (SD, 53.063) for IA and 5.009 (SD, 8.432) for HC. A cut-off >36.910 was chosen that performed with 100% specificity and sensitivity. Patients with PIA had either values above [53% (76/144)] or below [47% (67/144)] this chosen cut-off. The detection of respective reporter peptide fragments can easily be performed by MALDI TOF mass spectrometry. In this proof of concept study we were able to demonstrate that serum specimens of patients with IA have increased proteolytic activity towards selected reporter peptides. However, the diagnostic value of functional protease profiling has to be validated in further prospective studies. It is likely that a combination of existing and new methods will be required to achieve optimal performance for diagnosis of IA in the future.
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1 

Denning DW: Invasive aspergillosis. Clin Infect Dis. 26:781–803; quiz 804–805. 1998. View Article : Google Scholar : PubMed/NCBI

2 

Segal BH: Aspergillosis. N Engl J Med. 360:1870–1884. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Hohl TM and Feldmesser M: Aspergillus fumigatus: Principles of pathogenesis and host defense. Eukaryot Cell. 6:1953–1963. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Thompson GR III and Patterson TF: Pulmonary aspergillosis: Recent advances. Semin Respir Crit Care Med. 32:673–681. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Latgé JP: Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev. 12:310–350. 1999.PubMed/NCBI

6 

Hope WW, Walsh TJ and Denning DW: Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis. 5:609–622. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Adam O, Aupérin A, Wilquin F, Bourhis JH, Gachot B and Chachaty E: Treatment with piperacillin-tazobactam and false-positive Aspergillus galactomannan antigen test results for patients with hematological malignancies. Clin Infect Dis. 38:917–920. 2004. View Article : Google Scholar : PubMed/NCBI

8 

McCulloch E, Ramage G, Rajendran R, Lappin DF, Jones B, Warn P, Shrief R, Kirkpatrick WR, Patterson TF and Williams C: Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis. J Clin Pathol. 65:83–86. 2012. View Article : Google Scholar

9 

Barton RC: Laboratory diagnosis of invasive aspergillosis: From diagnosis to prediction of outcome. Scientifica Cairo. 2013:4594052013.PubMed/NCBI

10 

Pickering JW, Sant HW, Bowles CA, Roberts WL and Woods GL: Evaluation of a (1–>3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol. 43:5957–5962. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Mennink-Kersten MASH, Warris A and Verweij PE: 1,3-β-D-glucan in patients receiving intravenous amoxicillin-clavulanic acid. N Engl J Med. 354:2834–2835. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Einsele H and Loeffler J: Contribution of new diagnostic approaches to antifungal treatment plans in high-risk haematology patients. Clin Microbiol Infect. 14(Suppl 4): 37–45. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Kogan TV, Jadoun J, Mittelman L, Hirschberg K and Osherov N: Involvement of secreted Aspergillus fumigatus proteases in disruption of the actin fiber cytoskeleton and loss of focal adhesion sites in infected A549 lung pneumocytes. J Infect Dis. 189:1965–1973. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Jambunathan K, Watson DS, Najvar LK, Wiederhold NP, Kirkpatrick WR, Patterson TF, Askew DS, Kodukula K and Galande AK: Prolyl endopeptidase activity in bronchoalveolar lavage fluid: A novel diagnostic biomarker in a guinea pig model of invasive pulmonary aspergillosis. Med Mycol. 51:592–602. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Findeisen P, Post S, Wenz F and Neumaier M: Addition of exogenous reporter peptides to serum samples before mass spectrometry-based protease profiling provides advantages over profiling of endogenous peptides. Clin Chem. 53:1864–1866. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Peccerella T, Lukan N, Hofheinz R, Schadendorf D, Kostrezewa M, Neumaier M and Findeisen P: Endoprotease profiling with double-tagged peptide substrates: A new diagnostic approach in oncology. Clin Chem. 56:272–280. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Findeisen P, Costina V, Yepes D, Hofheinz R and Neumaier M: Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: Demonstration of its routine diagnostic applicability. J Exp Clin Cancer Res. 31:562012. View Article : Google Scholar : PubMed/NCBI

18 

De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, et al: European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group: Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 46:1813–1821. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Ostrosky-Zeichner L: Invasive mycoses: Diagnostic challenges. Am J Med. 125(Suppl): S14–S24. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Schaal R, Kupfahl C, Buchheidt D, Neumaier M and Findeisen P: Systematic identification of substrates for profiling of secreted proteases from Aspergillus species. J Microbiol Methods. 71:93–100. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Neustadt M, Costina V, Kupfahl C, Buchheidt D, Eckerskorn C, Neumaier M and Findeisen P: Characterization and identification of proteases secreted by Aspergillus fumigatus using free flow electrophoresis and MS. Electrophoresis. 30:2142–2150. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Watson DS, Feng X, Askew DS, Jambunathan K, Kodukula K and Galande AK: Substrate specifity profiling of the Aspergillus fumigatus proteolytic secretome reveals consensus motifs with predominance of Ile/Leu and Phe/Tyr. PLoS One. 6:e210012011. View Article : Google Scholar : PubMed/NCBI

23 

Rawlings ND, Morton FR, Kok CY, Kong J and Barrett AJ: MEROPS: The peptidase database. Nucleic Acids Res. 36:Database. D320–D325. 2008. View Article : Google Scholar :

24 

Findeisen P, Costina V, Yepes D, Hofheinz R and Neumaier M: Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: Demonstration of its routine diagnostic applicability. J Exp Clin Cancer Res. 31:562012. View Article : Google Scholar : PubMed/NCBI

25 

Vaideeswar P, Prasad S, Deshpande JR and Pandit SP: Invasive pulmonary aspergillosis: A study of 39 cases at autopsy. J Postgrad Med. 50:21–26. 2004.PubMed/NCBI

26 

Findeisen P and Neumaier M: Functional protease profiling for diagnosis of malignant disease. Proteomics Clin Appl. 6:60–78. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Witt I: Test systems with synthetic peptide substrates in haemostaseology. Eur J Clin Chem Clin Biochem. 29:355–374. 1991.PubMed/NCBI

28 

Powell MF, Grey H, Gaeta F, Sette A and Colón S: Peptide stability in drug development: A comparison of peptide reactivity in different biological media. J Pharm Sci. 81:731–735. 1992. View Article : Google Scholar : PubMed/NCBI

29 

Walker JR, Altman RK, Warren JW and Altman E: Using protein-based motifs to stabilize peptides. J Pept Res. 62:214–226. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Donnelly JP: Consensus definitions for invasive fungal disease: Strengths, limitations, and revisions. Med Mycol. 44(s1): 285–288. 2006. View Article : Google Scholar

31 

Subirà M, Martino R, Franquet T, Puzo C, Altés A, Sureda A, Brunet S and Sierra J: Invasive pulmonary aspergillosis in patients with hematologic malignancies: Survival and prognostic factors. Haematologica. 87:528–534. 2002.PubMed/NCBI

32 

Subirà M, Martino R, Rovira M, Vazquez L, Serrano D and De La Cámara R: Clinical applicability of the new EORTC/MSG classification for invasive pulmonary aspergillosis in patients with hematological malignancies and autopsy-confirmed invasive aspergillosis. Ann Hematol. 82:80–82. 2003.PubMed/NCBI

33 

Tsitsikas DA, Morin A, Araf S, Murtagh B, Johnson G, Vinnicombe S, Ellis S, Suaris T, Wilks M, Doffman S, et al: Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis. Med Mycol. 50:538–542. 2012. View Article : Google Scholar

34 

Johnson G, Ferrini A, Dolan SK, Nolan T, Agrawal S, Doyle S and Bustin SA: Biomarkers for invasive aspergillosis: The challenges continue. Biomarkers Med. 8:429–451. 2014. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Sabbagh B, Costina V, Buchheidt D, Reinwald M, Neumaier M and Findeisen P: Functional protease profiling for laboratory based diagnosis of invasive aspergillosis. Int J Oncol 47: 143-150, 2015.
APA
Sabbagh, B., Costina, V., Buchheidt, D., Reinwald, M., Neumaier, M., & Findeisen, P. (2015). Functional protease profiling for laboratory based diagnosis of invasive aspergillosis. International Journal of Oncology, 47, 143-150. https://doi.org/10.3892/ijo.2015.2984
MLA
Sabbagh, B., Costina, V., Buchheidt, D., Reinwald, M., Neumaier, M., Findeisen, P."Functional protease profiling for laboratory based diagnosis of invasive aspergillosis". International Journal of Oncology 47.1 (2015): 143-150.
Chicago
Sabbagh, B., Costina, V., Buchheidt, D., Reinwald, M., Neumaier, M., Findeisen, P."Functional protease profiling for laboratory based diagnosis of invasive aspergillosis". International Journal of Oncology 47, no. 1 (2015): 143-150. https://doi.org/10.3892/ijo.2015.2984
Copy and paste a formatted citation
x
Spandidos Publications style
Sabbagh B, Costina V, Buchheidt D, Reinwald M, Neumaier M and Findeisen P: Functional protease profiling for laboratory based diagnosis of invasive aspergillosis. Int J Oncol 47: 143-150, 2015.
APA
Sabbagh, B., Costina, V., Buchheidt, D., Reinwald, M., Neumaier, M., & Findeisen, P. (2015). Functional protease profiling for laboratory based diagnosis of invasive aspergillosis. International Journal of Oncology, 47, 143-150. https://doi.org/10.3892/ijo.2015.2984
MLA
Sabbagh, B., Costina, V., Buchheidt, D., Reinwald, M., Neumaier, M., Findeisen, P."Functional protease profiling for laboratory based diagnosis of invasive aspergillosis". International Journal of Oncology 47.1 (2015): 143-150.
Chicago
Sabbagh, B., Costina, V., Buchheidt, D., Reinwald, M., Neumaier, M., Findeisen, P."Functional protease profiling for laboratory based diagnosis of invasive aspergillosis". International Journal of Oncology 47, no. 1 (2015): 143-150. https://doi.org/10.3892/ijo.2015.2984
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