Research for the Environment

Mass spectrometry-based diagnostics of pathogenic dermatophytes

According to an official estimate, about 8 Mio. people in Germany alone suffer from mycosis of the skin and nail. Due to the surprisingly high number of about 80 to 100 different relevant fungal pathogens, the quest for an effective therapy is of paramount interest, as several of the different species of fungus display varying sensitivities towards the diverse antimycotics available. Thus, preceding the prescription of a locally or systemically acting drug, the correct diagnosis with accompanying species identification is of particular importance. Unfortunately, current diagnostic methods often reveal their limitations, with culturing of the pathogen representing a time-consuming and error-prone procedure, whereas histological findings do not permit the determination of the envolved species.

The aim of this project is the development and implementation of a rapid and reliable method for species determination of dermatopathogenic fungi by mass spectrometry. For this, protein and peptide spectra will be aquired by Intact Protein Profiling (IPP) and Shotgun Mass Mapping (SMM) for all relevant dermatophytes, using material from cultured organisms. Species-specific, unique peptides can be obtained by comparison of the respective spectra.

Due to its speed, its high sensitivity and specificity as well as its potential for automatization, the method of mass spectrometry-based diagnostics presented here could mature into a cost-efficient, high-throughput method of interest for other diagnostic challenges in the near future.

publications

Kliemt S, Lange C, Otto W, Hintze V, Möller S, von Bergen M, Hempel U, Kalkhof S.
Sulfated hyaluronan containing collagen matrices enhance cell-matrix-interaction, endocytosis, and osteogenic differentiation of human mesenchymal stromal cells.
J Proteome Res. 2012 Nov 21. [Epub ahead of print] PMID:23170904

Haange SB, Oberbach A, Schlichting N, Hugenholtz F, Smidt H, von Bergen M, Till H, Seifert J.
Metaproteome analysis and molecular genetics of rat intestinal microbiota reveals section and localisation resolved species distribution and enzymatic functionalities.
J Proteome Res. 2012 Nov 2;11(11):5406-17. PMID: 23016992

Müller SA, van der Smissen A, von Feilitzsch M, Anderegg U, Kalkhof S, von Bergen M.
Quantitative proteomics reveals altered expression of extracellular matrix related proteins of human primary dermal fibroblasts in response to sulfated hyaluronan and collagen applied as artificial extracellular matrix.
J Mater Sci Mater Med. 2012 Dec;23(12):3053-65. PMID: 22990618

Goettsch C, Kliemt S, Sinningen K, von Bergen M, Hofbauer LC, Kalkhof S.
Quantitative proteomics reveals novel functions of osteoclast-associated receptor in STAT signaling and cell adhesion in human endothelial cells.
J Mol Cell Cardiol. 2012 Dec;53(6):829-37. PMID: 22985931

Salbach J, Kliemt S, Rauner M, Rachner TD, Goettsch C, Kalkhof S, von Bergen M, Möller S, Schnabelrauch M, Hintze V, Scharnweber D, Hofbauer LC.
The effect of the degree of sulfation of glycosaminoglycans on osteoclast function and signaling pathways.
Biomaterials 2012 Nov;33(33):8418-29. PMID: 22954516

Guazzaroni ME, Herbst FA, Lores I, Tamames J, Peláez AI, López-Cortés N, Alcaide M, Del Pozo MV, Vieites JM, von Bergen M, Gallego JL, Bargiela R, López-López A, Pieper DH, Rosselló-Móra R, Sánchez J, Seifert J, Ferrer M.
Metaproteogenomic insights beyond bacterial response to naphthalene exposure and bio-stimulation.
ISME J. 2012 Jul 26. doi: 10.1038/ismej.2012.82.[Epub ahead of print] PMID: 22832345

Taubert M, Vogt C, Wubet T, Kleinsteuber S, Tarkka MT, Harms H, Buscot F, Richnow HH, von Bergen M, Seifert J
Protein-SIP enables time-resolved analysis of the carbon flux in a sulfate-reducing, benzene-degrading microbial consortium.
ISME J. 2012 Jul 12. doi: 10.1038/ismej.2012.68. [Epub ahead of print] PMID: 22791237.


Boll K, Reiche K, Kasack K, Mörbt N, Kretzschmar AK, Tomm JM, Verhaegh G, Schalken J, von Bergen M, Horn F, Hackermüller J.
MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma.
Oncogene. 2012 Mar 5. doi: 10.1038/onc.2012.55. [Epub ahead of print] PubMed PMID: 22391564.


Haas S, Jahnke HG, Moerbt N, von Bergen M, Aharinejad S, Andrukhova O, Robitzki AA
DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for studying cellular response to acute ischemia and regeneration.
PLoS One. 2012;7(2):e31669. Epub 2012 Feb 22. PubMed PMID: 22384053