Project Z2
Quantitative 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.
Principal Investigators
Prof. Dr. Ferdinand von Eggeling
Jena University Hospital, ENT Department
Friedrich Schiller University Jena
Publications
| Author | Year | Title | Journal | Links |
|---|---|---|---|---|
| Pinzan CF, Valero C, de Castro PA, da Silva JL, Earle K, Liu H, Horta MAC, Kniemeyer O, Krüger T, Pschibul A, Cömert DN, Heinekamp T, Brakhage AA, Steenwyk JL, Mead ME, Hermsdorf N, Filler SG, da Rosa-Garzon NG, Delbaje E, Bromley MJ, Cabral H, Diehl C, Angeli CB, Palmisano G, Ibrahim AS, Rinker DC, Sauters TJC, Steffen K, Gumilang A, Rokas A, Gago S, Dos Reis TF, Goldman GH | 2024 | Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation. | Nat Microbiol. | PubMed |
| Dellière S, Chauvin C, Wong SSW, Gressler M, Possetti V, Parente R, Fontaine T, Krüger T, Kniemeyer O, Bayry J, Carvalho A, Brakhage AA, Inforzato A, Latgé JP, Aimanianda V. | 2024 | Interplay between host humoral pattern recognition molecules controls undue immune responses against Aspergillus fumigatus. | Nat Commun. 15(1):6966 | PubMed |
| Günther K, Nischang V, Cseresnyés Z, Krüger T, Sheta D, Abboud Z, Heinekamp T, Werner M, Kniemeyer O, Beilhack A, Figge MT, Brakhage AA, Werz O, Jordan PM | 2024 | Aspergillus fumigatus-derived gliotoxin impacts innate immune cell activation through modulating lipid mediator production in macrophages. | Immunology. | PubMed |
| Müller R, König A, Groth S, Zarnowski R, Visser C, Handrianz T, Maufrais C, Krüger T, Himmel M, Lee S, Priest EL, Yildirim D, Richardson JP, Blango MG, Bougnoux ME, Kniemeyer O, d'Enfert C, Brakhage AA, Andes DR, Trümper V, Nehls C, Kasper L, Mogavero S, Gutsmann T, Naglik JR, Allert S, Hube B | 2024 | Secretion of the fungal toxin candidalysin is dependent on conserved precursor peptide sequences. | Nat Microbiol. (3):669-683. | PubMed |
| van Rhijn N, Zhao C, Al-Furaji N, Storer ISR, Valero C, Gago S, Chown H, Baldin C, Grant RF, Bin Shuraym H, Ivanova L, Kniemeyer O, Krüger T, Bignell E, Goldman GH, Amich J, Delneri D, Bowyer P, Brakhage AA, Haas H, Bromley MJ | 2024 | Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging. | Nat Commun. 15(1):4984 | PubMed |
| Jia LJ, Rafiq M, Radosa L, Hortschansky P, Cunha C, Cseresnyés Z, Krüger T, Schmidt F, Heinekamp T, Straßburger M, Löffler B, Doenst T, Lacerda JF, Campos A, Figge MT, Carvalho A, Kniemeyer O, Brakhage AA | 2023 | Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway. | Cell Host & Microbe: 31,3 | Cell Host & Microbe |
| Kelani AA, Bruch A, Rivieccio F, Visser C, Krueger T, Weaver D, Pan X, Schaeuble S, Panagiotou G, Kniemeyer O, Bromley MJ, Bowyer P, Barber AE, Brakhage AA, Blango MG. | 2023 | Disruption of the Aspergillus fumigatus RNA interference machinery alters the conidial transcriptome. | RNA [Epub ahead of print] | PubMed |
| Sala A, Ardizzoni A, Spaggiari L, Vaidya N, van der Schaaf J, Rizzato C, Cermelli C, Mogavero S, Krüger T, Himmel M, Kniemeyer O, Brakhage AA, King BL, Lupetti A, Comar M, de Seta F, Tavanti A, Blasi E, Wheeler RT, Pericolini E. A | 2023 | New Phenotype in Candida-Epithelial Cell Interaction Distinguishes Colonization- versus Vulvovaginal Candidiasis-Associated Strains. | mBio 3: e0010723 | PubMed |
| Krespach MKC, Stroe MC, Netzker T, Rosin M, Zehner LM, Komor AJ, Beilmann JM, Krüger T, Scherlach K, Kniemeyer O, Schroeckh V, Hertweck C, Brakhage AA | 2023 | Streptomyces polyketides mediate bacteria–fungi interactions across soil environments. | Nature Microbiology | Nat Microb |
| Garloff V, Krüger T, Brakhage A, Rubio I. | 2023 | Control of TurboID-dependent biotinylation intensity in proximity ligation screens. J Proteomics. | J Proteomics 15;279:104886 | PubMed |
| Wein P, Dornblut K, Herkersdorf S, Krüger T, Molloy EM, Brakhage AA, Hoffmeister D, Hertweck C | 2023 | Bacterial secretion systems contribute to rapid tissue decay in button mushroom soft rot disease. | mBio: e0078723 | PubMed |
| Sala A, Ardizzoni A, Spaggiari L, Vaidya N, van der Schaaf J, Rizzato C, Cermelli C, Mogavero S, Krüger T, Himmel M, Kniemeyer O, Brakhage AA, King BL, Lupetti A, Comar M, de Seta F, Tavanti A, Blasi E, Wheeler RT, Pericolini E | 2023 | A new phenotype in Candida-epithelial cell interaction distinguishes colonization-versus culvovaginal candidiasis-associated strains. | mBio 14(2), e0010723 | PubMed |
| Ramírez-Zavala B, Betsova D, Schwanfelder S, Krüger I, Mottola A, Krüger T, Kniemeyer O, Brakhage AA, Morschhäuser J. | 2023 | Multiple phosphorylation sites regulate the activity of the repressor Mig1 in Candida albicans. | mSphere: 8 (6) | PubMed |
| Schruefer S, Pschibul A, Wong SSW, Sae-Ong T, Wolf T, Schäuble S, Panagiotou G, Brakhage AA, Aimanianda V, Kniemeyer O, Ebel F | 2023 | Distinct transcriptional responses to fludioxonil in Aspergillus fumigatus and its ΔtcsC and Δskn7 mutants reveal a crucial role for Skn7 in the cell wall reorganizations triggered by this antifungal. | BMC Genomics. 14;24(1):684 | PubMed |
| Rafiq M, Rivieccio F, Zimmermann AK, Visser C, Bruch A, Krüger T, González Rojas K, Kniemeyer O, Blango MG, Brakhage AA | 2022 | PLB-985 neutrophil-like cells as a model to study Aspergillus fumigatus pathogenesis. | mSphere e0094021 | PubMed |
| Brandt P, Gerwien F, Wagner L, Krüger T, Ramirez-Zavala B, Mirhakkak MH, Schäuble S, Kniemeyer O, Panagiotou G, Brakhage AA, Morschhäuser J, Vylkova S | 2022 | Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization. | Frontiers Cellular Infection Microbiology doi:0.3389/fcimb.2022.850531 | Front. Cell. Infect. Microbiol. |
| Niemiec MJ, Kapitan M, Himmel M, Döll K, Krüger T, Köllner TG, Auge I, Kage F, Alteri CJ, Mobley HLT, Monsen T, Linde S, Nietzsche S, Kniemeyer O, Brakhage AA, Jacobsen ID | 2022 | Augmented Enterocyte Damage During Candida albicans and Proteus mirabilis Coinfection. | Front Cell Infect Microbiol. 12:866416 | PubMed |
| Raguž L, Peng C, Rutaganira FUN, Krüger T, Stanisic A, Jautzus T, Kries H, Kniemeyer O, Brakhage AA, King N, Beemelmanns C | 2022 | Total Synthesis and Functional Evaluation of IORs, Sulfonolipid-based Inhibitors of Cell Differentiation in Salpingoeca rosetta | Angew. Chem. Int. Ed. e202209105 | Angew. Chem. Int. Ed. |
| Acosta España JD, Hassan MA, Hea-Reung P, Schwartze VU, Schäuble S, Krüger T, Kniemeyer O, Brakhage AA, Voigt K | 2022 | Novel hydrophobic binding surface proteins are instrumental for phagocytosis of Lichtheimia corymbifera by macrophages. | Medical Mycology 60 (1) :myac072P343 | Medical Mycology |
| Tappe B, Lauruschkat CD, Strobel L, Pantaleón García J, Kurzai O, Rebhan S, Kraus S, Pfeuffer-Jovic E, Bussemer L, Possler L, Held M, Hünniger K, Kniemeyer O, Schäuble S, Brakhage AA, Panagiotou G, White PL, Einsele H, Löffler J, Wurster S. | 2022 | COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds. | Front Immunol. 13: 954985 | PubMed |
| Böttcher B, Driesch D, Krüger T, Garbe E, Gerwien F, Kniemeyer O, Brakhage AA, Vylkova S | 2022 | Impaired amino acid uptake leads to global metabolic imbalance of Candida albicans biofilms. | NPJ Biofilms Microbiomes. 8(1): 78 | PubMed |
| de Assis LJ, Silva LP, Bayram O, Dowling P, Kniemeyer O, Krüger T, Brakhage AA, Chen Y, Dong L, Tan K, Wong KH, Ries LNA, Goldman GH | 2021 | Carbon catabolite repression in filamentous fungi is regulated by phosphorylation of the transcription factor CreA. | mBio 12: e03146-20 | PubMed |
| Strømland Ø, Kallio JP, Pschibul A, Skoge RH, Harðardóttir HM, Sverkeli LJ, Heinekamp T, Kniemeyer O, Migaud M, Makarov MV, Gossmann TI, Brakhage AA, Ziegler M | 2021 | Discovery of fungal surface NADases predominantly present in pathogenic species. | Nat Commun 12: 1631 | PubMed |
| Lauruschkat CD, Page L, White PL, Etter S, Davies HE, Duckers J, Ebel F, Schnack E, Backx M, Dragan M, Schlegel N, Kniemeyer O, Brakhage AA, Einsele H, Loeffler J, Wurster S | 2021 | Development of a simple and robust whole blood assay with dual co-stimulation to quantify the release of T-cellular signature cytokines in response to Aspergillus fumigatus antigens. | J Fungi 7: 462 | MDPI |
| Page L, Wallstabe J, Lother J, Bauser M, Kniemeyer O, Strobel L, Voltersen V, Teutschbein J, Hortschansky P, Morton CO, Brakhage AA, Topp M, Einsele H, Wurster S, Loeffler J | 2021 | CcpA- and Shm2-pulsed myeloid dendritic cells induce T-cell activation and enhance the neutrophilic oxidative burst response to Aspergillus fumigatus. | Front Immunol 12: 659752 | PubMed |
| Mogavero S, Sauer FM, Brunke S, Allert S, Schulz D, Wisgott S, Jablonowski N, Elshafee O, Krüger T, Kniemeyer O, Brakhage AA, Naglik JR, Dolk E, Hube B | 2021 | Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans. | Cell microbiol 23: e13378 | PubMed |
| Wich M, Greim S, Ferreira-Gomes M, Krüger T, Kniemeyer O, Brakhage AA, Jacobsen ID, Hube B, Jungnickel B | 2021 | Functionality of the human antibody response to Candida albicans. | Virulence 12: 3137-48 | PubMed |
| López-Berges MS, Scheven MT, Hortschansky P, Misslinger M, Baldin C, Gsaller F, Werner ER, Krüger T, Kniemeyer O, Weber J, Brakhage AA, Haas H | 2021 | The bZIP Transcription Factor HapX Is Post-Translationally Regulated to Control Iron Homeostasis in Aspergillus fumigatus. | Int J Mol Sci. 22(14): 7739 | PubMed |
| Radosa S, Sprague JL, Lau SH, Tóth R, Linde J, Krüger T, Sprenger M, Kasper L, Westermann M, Kniemeyer O, Hube B, Brakhage AA, Gácser A, Hillmann F | 2021 | The fungivorous amoeba Protostelium aurantium targets redox homeostasis and cell wall integrity during intracellular killing of Candida parapsilosis. | Cell Microbiol. 23(11): e13389 | PubMed |
| Shopova IA, Belyaev I, Dasari P, Jahreis S, Stroe MC, Cseresnyés Z, Zimmermann AK, Medyukhina A, Svensson CM, Krüger T, Szeifert V, Nietzsche S, Conrad T, Blango MG, Kniemeyer O, Lilienfeld-Toal Mv, Zipfel PF, Ligeti E, Figge MT, Brakhage AA | 2020 | Human neutrophils produce antifungal extracellular vesicles against Aspergillus fumigatus. | mBio 11: e00596-20 | PubMed |
| Halder LD, Jo EAH, Hasan MZ, Ferreira-Gomes M, Krüger T, Westermann M, Palme DI, Rambach G, Beyersdorf N, Speth C, Jacobsen ID, Kniemeyer O, Jungnickel B, Zipfel PF, Skerka C | 2020 | Immune modulation by complement receptor 3 dependent human monocyte TGF-β1-transporting vesicles. | Nat Commun 11: 2331 | PubMed |
| Blango MG, Pschibul A, Rivieccio F, Krüger T, Muhammad R, Jia L, Zheng T, Goldmann M, Voltersen V, Li Jun, Panagiotou G, Kniemeyer O, Brakhage AA | 2020 | Dynamic surface proteomes of allergenic fungal conidia. | J Proteome Res 19: 2092-104 | PubMed |
| Hassan MIA, Kruse J, Krüger T, Dahse HM, Cseresnyés Z, Blango MG, Slevogt H, Hörhold F, Ast V, König R, Figge MT, Kniemeyer O, Brakhage AA, Voigt K | 2020 | Functional surface proteomic profiling reveals the host heat-shock protein A8 as a mediator of Lichtheimia corymbifera recognition by murine alveolar macrophages. | Environ Microbiol 22: 3722-40 | PubMed |
| Ruben S, Garbe E, Mogavero S, Albrecht-Eckardt D, Hellwig D, Häder A, Krüger T, Gerth K, Jacobsen ID, Elshafee O, Brunke S, Hünniger K, Kniemeyer O, Brakhage AA, Morschhäuser J, Hube B, Vylkova S, Kurzai O, Martin R | 2020 | Ahr1 and Tup1 contribute to the transcriptional control of virulence-associated genes in Candida albicans. | mBio 11: e00206-20 | PubMed |
| Jia LJ, Krüger T, Blango MG, von Eggeling F, Kniemeyer O, Brakhage AA | 2020 | Biotinylated surfome profiling identifies potential biomarkers for diagnosis and therapy of Aspergillus fumigatus infection. | mSphere 5: e00535-20 | PubMed |
| Satish S, Jimenez-Ortigosa C, Zhao Y, Lee MH, Dolgov E, Krüger T, Park S, Denning DW, Kniemeyer O, Brakhage AA, Perlin DS | 2019 | Stress-induced changes in the lipid microenvironment of β-(1,3)-D-glucan synthase cause clinically important echinocandin resistance in Aspergillus fumigatus. | mBio 10: e00779-19 | PubMed |
| Bacher P, Hohnstein T, Beerbaum E, Röcker M, Kaufmann S, Brandt C, Röhmel J, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Heine G, Worm M, Creutz P, Tabeling C, Ruwwe-Glösenkamp C, Sander LE, Brunke S, Hube B, Blango M, Kniemeyer O, Brakhage AA, Schwarz C, Scheffold A | 2019 | Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. | Cell 176: 1340-55 | PubMed |
| Shekhova E, Ivanova L, Krüger T, Stroe MC, Macheleidt J, Kniemeyer O, Brakhage AA | 2019 | Redox proteomic analysis reveals oxidative modifications of proteins by increased levels of intracellular reactive oxygen species during hypoxia adaptation of Aspergillus fumigatus. | Proteomics 19: 1800339 | PubMed |
| Hoffmann F, Umbreit C, Krüger T, Pelzel D, Ernst G, Kniemeyer O, Guntinas-Lichius O, Berndt A, von Eggeling F | 2019 | Identification of proteomic markers in head and neck cancer using MALDI-MS imaging, LC-MS/MS, and immunohistochemistry. | Proteomics Clin Appl 13: e1700173 | PubMed |
| Schmidt H, Vlaic S, Krüger T, Schmidt F, Balkenhol 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: 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 |
| Conrad T, Kniemeyer O, Henkel SG, Krüger T, Mattern DJ, Valiante V, Guthke R, Jacobsen ID, Brakhage AA, Vlaic S, Linde J | 2018 | Module-detection approaches for the integration of multilevel omics data highlight the comprehensive response of Aspergillus fumigatus to caspofungin. | BMC Syst Biol 12: 88 | PubMed |
| Voltersen V, Blango MG, Herrmann S, Schmidt F, Heinekamp T, Strassburger M, Krüger T, Bacher P, Lother J, Weiss E, Hünniger K, Liu H, Hortschansky P, Scheffold A, Löffler J, Krappmann S, Nietzsche S, Kurzai O, Einsele H, Kniemeyer O, Filler SG, Reichard U, Brakhage AA | 2018 | Proteome analysis reveals the conidial surface protein CcpA essential for virulence of the pathogenic fungus Aspergillus fumigatus. | mBio 9: e01557-18 | 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: 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 |