Project C2

Regulation of Candida albicans virulence traits by protein kinases

The reversible phosphorylation of effector proteins is a common mechanism to trigger cellular reactions in response to extracellular and intracellular signals in all organisms. The aim of project C2 is a comprehensive functional analysis of all protein kinases of the human-pathogenic yeast C. albicans to gain insight into their role and importance for the adaptation of this fungal pathogen to different environmental conditions during colonization and infection of its host.

Principal Investigators
Author Year Title Journal Links
Schimanski J, Gresnigt MS, Brunner E, Werz O, Hube B, Garscha U 2024 Hyphal-associated protein expression is crucial for Candida albicans-induced eicosanoid biosynthesis in immune cells. Eur J Immunol:e2350743 PubMed
Böttcher B, Kienast SD, Leufken J, Eggers C, Sharma P, Leufken CM, Morgner B, Drexler HCA, Schulz D, Allert S, Jacobsen ID, Vylkova S, Leidel SA, Brunke S 2024 A highly conserved tRNA modification contributes to C. albicans filamentation and virulence. Microbiol Spectr. e0425522 PubMed
Garbe E, Thielemann N, Hohner S, Kumar A, Vylkova S, Kurzai O, Martin R. 2023 Functional analysis of the Candida albicans ECE1 Promoter. Microbiol Spectr: e0025323 PubMed
Brandt P, Mirhakkak MH, Wagner L, Driesch D, Möslinger A, Fänder P, Schäuble S, Panagiotou G, Vylkova S. 2023 High-Throughput Profiling of Candida auris Isolates Reveals Clade-Specific Metabolic Differences. Microbiol Spectrum : e0049823 PubMed
Häder, A, Schäuble, S, Gehlen, J, Thielemann N, Buerfent BC, Schüller V, Hess T, Wolf T, Schröer J, Weber M, Hünniger K, Löffler J, Vylkova S, Panagiotou G, Schumacher J, Kurzai O 2023 Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity. Nature Communications PubMed
Rebai, Y.; Wagner, L.; Gnaien, M.; Hammer, M.L.; Kapitan, M.; Niemiec, M.J.; Mami, W.; Mosbah, A.; Messadi, E.; Mardassi, Vylkova S, Jacobsen ID, Znaidi S. 2023 Escherichia coli Nissle 1917 Antagonizes Candida albicans Growth and Protects Intestinal Cells from C. albicans-Mediated Damage. Microorganisms 11, 1929 Microorganisms
Oneissi M, Cruz MR, Ramírez-Zavala B, Lindemann-Perez E, Morschhäuser J, Garsin DA, Perez JC 2023 Host-derived reactive oxygen species trigger activation of the Candida albicans transcription regulator Rtg1/3 PLoS Pathog. 19(9) PLoS Pathog.
Ramírez-Zavala B, Krüger I, Wollner A, Schwanfelder S, Morschhäuser J 2023 The Ypk1 protein kinase signaling pathway is rewired and not essential for viability in Candida albicans. PLoS Genet. 19(8):e1010890 PubMed
Luther CH, Brandt P, Vylkova S, Dandekar T, Müller T, Dittrich M 2023 Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans. Front Cell Infect Microbiol.13:1108235 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
Ramírez-Zavala B, Krüger I, Dunker C, Jacobsen ID, Morschhäuser J 2022 The protein kinase Ire1 has a Hac1-independent essential role in iron uptake and virulence of Candida albicans. PLoS Pathog 18(2): e1010283 PubMed
Garbe E, Miramón P, Gerwien F, Ueberschaar N, Hansske-Braun L, Brandt P, Böttcher B, Lorenz M, Vylkova S 2022 GNP2 Encodes a High-Specificity Proline Permease in Candida albicans. mBio 13(1): e0314221 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.
Alonso-Roman R, Last A, Mirhakkak MH, Spraque JL, Möller L, Großmann P, Graf K, Gratz R, Mogavero S, Vylkova S, Panagiotou G, Schäuble S, Hube B, Gresnigt MS 2022 Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity. Nat. Commun. 13, 3192 Nat. Commun.
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
Ramírez-Zavala B, Mottola A, Krüger I, Morschhäuser J 2021 A suppressor mutation in the β-subunit Kis1 restores functionality of the SNF1 complex in Candida albicans snf4Δ Mutants. mSphere 6: e0092921 PubMed
Mottola A, Ramírez-Zavala B, Hünniger K, Kurzai O, Morschhäuser J 2021 The zinc cluster transcription factor Czf1 regulates cell wall architecture and integrity in Candida albicans. Mol Microbiol. 116(2): 483-497. PubMed
Böttcher B, Hoffmann B, Garbe E, Weise T, Cseresnyés Z, Brandt P, Dietrich S, Driesch D, Figge MT, Vylkova S 2020 The transcription factor Stp2 is important for Candida albicans biofilm establishment and sustainability. Front Microbiol 11: 794 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
Gerwien F, Dunker C, Brandt P, Garbe E, Jacobsen ID, Vylkova S 2020 Clinical Candida albicans vaginal isolates and a laboratory strain show divergent behaviors during macrophage interactions. mSphere 5: e00393-20 PubMed
Brandt P, Garbe E, Vylkova S 2020 Catch the wave: Metabolomic analyses in human pathogenic fungi. PLoS Pathog 16: e1008757 (Review) PubMed
Mottola A, Schwanfelder S, Morschhäuser J 2020 Generation of viable Candida albicans mutants lacking the “essential” protein kinase Snf1 by inducible gene deletion. mSphere 5: e00805-20 PubMed
Mirhakkak MH, Schäuble S, Klassert TE, Brunke S, Brandt P, Loos D, Uribe RV, Senne de Oliveira Lino F, Ni Y, Vylkova S, Slevogt H, Hube B, Weiss GJ, Sommer MOA, Panagiotou G 2020 Metabolic modeling predicts specific gut bacteria as key determinants for Candida albicans colonization levels. ISME J 15: 1257-70 PubMed
von Müller C, Bulman F, Wagner L, Rosenberger D, Marolda A, Kurzai O, Eißmann P, Jacobsen ID, Perner B, Hemmerich P, Vylkova S 2020 Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants. Sci Rep 10: 21818 PubMed
Mottola A, Morschhäuser J 2019 An intragenic recombination event generates a Snf4-independent form of the essential protein kinase Snf1 in Candida albicans. mSphere 4: e00352-19 Pubmed
Popp C, Ramírez-Zavala B, Schwanfelder S, Krüger I, Morschhäuser J 2019 Evolution of fluconazole-resistant Candida albicans strains by drug-induced mating competence and parasexual recombination. mBio 10: e02740-18 PubMed
Ramírez-Zavala B, Manz H, Englert F, Rogers PD, Morschhäuser J 2018 A hyperactive form of the zinc cluster transcription factor Stb5 causes YOR1 overexpression and beauvericin resistance in Candida albicans. Antimicrob Agents Chemother 62: e01655-18 PubMed
Allert S*, Förster TM*, Svensson CM, Richardson JP, Pawlik T, Hebecker B, Rudolphi S, Juraschitz M, Schaller M, Blagojevic M, Morschhäuser J, Figge MT, Jacobsen ID, Naglik JR, Kasper L, Mogavero S, Hube B; *authors contributed equally 2018 Candida albicans-induced epithelial damage mediates translocation through intestinal barriers. mBio 9: e00915-18 PubMed
Ramírez-Zavala B, Mottola A, Haubenreißer J, Schneider S, Allert S, Brunke S, Ohlsen K, Hube B, Morschhäuser J 2017 The Snf1-activating kinase Sak1 is a key regulator of metabolic adaptation and in vivo fitness of Candida albicans. Mol Microbiol 104: 989-1007 PubMed
Hampe IAI, Friedman J, Edgerton M, Morschhäuser J 2017 An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses. PLoS Pathog 13: e1006655 PubMed
Morschhäuser J 2016 The development of fluconazole resistance in Candida albicans - an example of microevolution of a fungal pathogen. J Microbiol 54: 192-201 PubMed