Project Z2

Quantiative methods for the analysis of the spatial and temporal dynamic changes of the proteome during host-pathogen interaction

Based on the progress achieved in the area of mass spectrometry, proteomics, the large-scale study of proteins, has evolved into a powerful approach that enables quantification of several thousand proteins from a microorganism on a global scale. Proteomics is therefore one of the keystones of systems biology approaches which describe host-pathogen interactions. Project Z2 provides a sophisticated proteome analysis platform to specific A (Aspergillus) and C (Candida) projects of the CRC/TR FungiNet. The portfolio of proteome techniques includes 2D-gel electrophoresis and LC-MS/MS-based shotgun proteomic methods for identifying and quantifying the proteome of an organism on the level of peptides (“bottom-up” approach). Furthermore, we have established a serological proteome analysis method for the characterization of fungal protein antigens. In this funding period, our aim is to broaden the portfolio of proteomic methods. These include metabolic labeling, the investigation of different post-translational modifications (phosphorylation, acetylation, ubiquitination, protein thiol oxidation), absolute quantification of proteins based on quantifier peptides and subcellular fractionation (for example vesicles) to improve the dynamic range of proteome analyses. With MALDI MS Imaging (MSI) we are now able to analyze the spatial distribution of low molecular weight compounds like secondary metabolites, toxins and proteins in the interaction of the fungal pathogen and the host.

Methods for the proteomic analysis of host-fungal pathogen interactions.
Methods for the proteomic analysis of host-fungal pathogen interactions.
Principal Investigators
Dr. Olaf Kniemeyer
Dr. Olaf Kniemeyer

Department of Molecular and Applied Microbiology

Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute  

olaf.kniemeyer@leibniz-hki.de

PD Dr. Ferdinand von Eggeling
Prof. Dr. Ferdinand von Eggeling

Institute of Physical Chemistry

Friedrich Schiller University Jena

ferdinand.von_eggeling@med.uni-jena.de

Publications
Author Year Title Journal Links
Schmidt H, Vlaic S, Krüger T, Schmidt F, Balkenhohl J, Dandekar T, Guthke R, Kniemeyer O, Heinekamp T, Brakhage AA 2018 Proteomics of Aspergillus fumigatus conidia-containing phagolysosomes identifies processes governing immune evasion. Mol Cell Proteomics 17: 1084-96 PubMed
Richardson JP, Mogavero S, Moyes DL, Blagojevic M, Krüger T, Verma AH, Coleman BM, De La Cruz Diaz J, Schulz D, Ponde NO, Carrano G, Kniemeyer O, Wilson D, Bader O, Enoiu SI, Ho J, Kichik N, Gaffen SL, Hube B, Naglik J 2018 Processing of Candida albicans Ece1p is critical for Candidalysin maturation and fungal virulence. mBio 9: pii: e02178-17 PubMed
Kurucz V, Krüger T, Antal K, Dietl AM, Haas H, Pócsi I, Kniemeyer O, Emri T 2018 Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion. BMC Genomics 19: 357 PubMed
Pohlers S, Martin R, Krüger T, Hellwig D, Hänel F, Kniemeyer O, Saluz HP, Van Dijck P, Ernst JF, Brakhage A, Mühlschlegel FA, Kurzai O 2017 Lipid Signaling via Pkh1/2 regulates fungal CO2 sensing through the kinase Sch9. mBio 8 pii: e02211-16 PubMed
Teutschbein J, Simon S, Lother J, Springer J, Hortschansky P, Morton CO, Löffler J, Einsele H, Conneally E, Rogers TR, Guthke R, Brakhage AA, Kniemeyer O 2016 Proteomic profiling of serological responses to Aspergillus fumigatus antigens in patients with invasive aspergillosis. J Proteome Res 15: 1580-91 PubMed
Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J, Höfs S, Gratacap RL, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Förster TM, Hebecker B, Kasper L, Vizcay G, Iancu SI, Kichik N, Häder A, Kurzai O, Luo T, Krüger T, Kniemeyer O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B, Naglik JR 2016 Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532: 64-8 PubMed
Bacher P, Heinrich F, Stervbo U, Nienen M, Vahldieck M, Iwert C, Vogt K, Kollet J, Babel N, Sawitzki B, Schwarz C, Bereswill S, Heimesaat MM, Heine G, Gadermaier G, Asam C, Assenmacher M, Kniemeyer O, Brakhage AA, Ferreira F, Wallner M, Worm M, Scheffold A 2016 Regulatory T cell specificity directs tolerance versus allergy against aeroantigens in humans. Cell 167: 1067-78.e16 PubMed
Luo T, Krüger T, Knüpfer U, Kasper L, Wielsch N, Hube B, Kortgen A, Bauer M, Giamarellos-Bourboulis EJ, Dimopoulos G, Brakhage AA, Kniemeyer O 2016 Immunoproteomic analysis of antibody responses to extracellular proteins of Candida albicans revealing the importance of glycosylation for antigen recognition. J Proteome Res 15: 2394-406 PubMed
Kniemeyer O, Ebel F, Krüger T, Bacher P, Scheffold A, Luo T, Strassburger M, Brakhage AA 2016 Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies. Proteomics Clin Appl 10: 910-21 PubMed
Baldin C, Valiante V, Krüger T, Schafferer L, Haas H, Kniemeyer O, Brakhage AA 2015 Comparative proteomics of a tor inducible Aspergillus fumigatus mutant reveals involvement of the tor kinase in iron regulation. Proteomics 15: 2230-43 PubMed
Altwasser R, Baldin C, Weber J, Guthke R, Kniemeyer O, Brakhage AA, Linde J, Valiante V 2015 Network modeling reveals cross talk of MAP kinases during adaptation to caspofungin stress in Aspergillus fumigatus. PLoS One 10: e0136932 PubMed
Krüger T, Luo T, Schmidt H, Shopova I, Kniemeyer O 2015 Challenges and strategies for proteome analysis of the interaction of human pathogenic fungi with host immune cells. Proteomes 3: 467-95 PubMed
Heinekamp T, Schmidt H, Lapp K, Pähtz V, Shopova I, Köster-Eiserfunke N, Krüger T, Kniemeyer O, Brakhage AA 2015 Interference of Aspergillus fumigatus with the immune response. Semin Immunopathol 37: 141-52 PubMed
Hillmann F, Linde J, Beckmann N, Cyrulies M, Strassburger M, Heinekamp T, Haas H, Guthke R, Kniemeyer O, Brakhage AA 2014 The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus. Mol Microbiol 93: 539-53 PubMed
Lapp K, Vödisch M, Kroll K, Strassburger M, Kniemeyer O, Heinekamp T, Brakhage AA 2014 Characterisation of the Aspergillus fumigatus detoxification systems for reactive nitrogen intermediates and impact on virulence. Front Microbiol 5: 469 PubMed