Host Fungal Interfaces
The fungus Candida albicans is a commensal microorganism in humans mainly associated with mucosal surfaces, i.e. the oral cavity, the gastrointestinal and the urogenital tract, and the skin. Under certain circumstances, such as immune suppression or disruptions of the associated microbiota, it can become pathogenic and cause a range of infections: from mild inflammation of the skin or mucosal surfaces to severe invasive infections and sepsis. In order to survive and proliferate in the human host, this opportunistic fungal pathogen has acquired a remarkable repertoire of adaptation strategies to circumvent the host immune response and to cope with the limited nutrient supply and environmental alterations of pH, oxygen and osmolarity.
Metabolism is integral to C. albicans pathogenicity, since it provides the platform for nutrient assimilation and growth in diverse host niches and affects fungal susceptibility to stress conditions and antifungal drugs, the expression of key virulence factors, and fungal vulnerability to innate immune defenses. Another important pathogenicity factor is the ability to switch morphologies from the rounded yeast form to elongated hyphal form.
In the host C. albicans colonizes biotic and abiotic surfaces (e.g. catheters and prosthetic devices) primarily in the form of biofilm, a dense network of yeast and hyphal cells encased in extracellular matrix. Biofilm cells are highly resistant to antibiotics and therefore could serve as a reservoir of bloodstream infections or as a scaffold for growth of other pathogenic species. Importantly, Candida biofilm growth is linked to activation of the tricarboxylic acid (TCA) cycle and amino acid metabolism.
The junior research group Host Fungal Interfaces investigates adaptation mechanisms of C. albicans, which are driven by complex regulatory networks that link metabolism, hyphal morphogenesis, and responses to environmental stressors, all contributing to the successful colonization and pathogenicity of the fungus. Since hyphal morphogenesis and metabolic changes are critical for biofilm formation and sustainability, we aim to understand the role of nutrient supply in Candida biofilm formation and infection.
Head
Slavena Vylkova, PhD
Head
Publications
Alonso-Roman R, Last A, Mirhakkak MH, Sprague 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(1), 3192.
Brandt P, Gerwien F, Wagner L, Krüger T, Ramírez-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. Front Cell Infect Microbiol 12, 850531.
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, e0314221.
Mirhakkak M, Schäuble S, Klassert T, Brunke S, Brandt P, Loos D, Uribe R, de Oliveira Lino FS, Ni Y, Vylkova S, Slevogt H, Hube B, Weiss G, Sommer M, Panagiotou G (2021) Metabolic modeling predicts specific gut bacteria as key determinants for Candida albicans colonization levels. ISME J 15(5), 1257-1270.
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(1), 21818.
Wagner L, Bloos F, Vylkova S (2020) Bloodstream infection due to Enterobacter ludwigii, correlating with massive aggregation on the surface of a central venous catheter. Infection. doi: 10.1007/s15010-020-01482-9.
Kämmer P, McNamara S*, Wolf T, Conrad T, Allert S, Gerwien F, Hünniger K, Kurzai O, Guthke R, Hube B, Linde J, Brunke S (2020) Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. mBio 11(5), e02435-20.
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(4), e00393-20.
Brandt P, Garbe E, Vylkova S (2020) Catch the wave: Metabolomic analyses in human pathogenic fungi. PLoS Pathog 16(8), e1008757. (Review)
Wagner L, Stielow JB, de Hoog GS, Bensch K, Schwartze VU, Voigt K, Alastruey-Izquierdo A, Kurzai O, Walther G (2020) A new species concept for the clinically relevant Mucor circinelloides complex. Persoonia 44, 67-97.
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.
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(2). pii: e00206-20. doi: 10.1128/mBio.00206-20.
Weise T, Böttcher B, Vylkova S. (2020) Bioflux Analysis. Protocols. doi:10.17504/protocols.io.bb7qirmw
Garbe E & Vylkova S. (2019) Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi. Current Clinical Microbiology Reports. 6:108–119.
Vylkova S (2017) Environmental pH modulation by pathogenic fungi as a strategy to conquer the host. PloS Pathogens1 3(2), e1006149.
Vylkova S, Lorenz MC (2017) Phagosomal neutralization by the fungal pathogen Candida albicans induces macrophage pyroptosis. Infect Immun 85(2). pii: e00832-16.
Danhof HA, Vylkova S, Vesely EM, Ford AE, Gonzalez-Garay M, Lorenz MC (2016) Robust Extracellular pH Modulation by Candida albicans during Growth in Carboxylic Acids. mBio. 7(6).
Vylkova S, Lorenz MC (2014) Modulation of phagosomal pH by Candida albicans promotes hyphal morphogenesis and requires Stp2p, a regulator of amino acid transport. PLoS Pathog 10(3), e1003995.
Vylkova S, Carman AJ, Danhof HA, Collette JR, Zhou H, Lorenz MC (2011) The fungal pathogen Candida albicans autoinduces hyphal morphogenesis by raising extracellular pH. MBio 2(3), e00055.
Miranda M, Bashi E, Vylkova S, Edgerton M, Slayman C, Rivetta A (2009) Conservation and dispersion of sequence and function in fungal TRK potassium transporters: focus on Candida albicans. FEMS Yeast Res 9(2):278-292.
Carman AJ, Vylkova S, Lorenz MC (2008) Role of acetyl coenzyme A synthesis and breakdown in alternative carbon source utilization in Candida albicans. Eukaryot Cell 7(10):1733-1741.
Vylkova S, Jang WS, Li W, Nayyar N, Edgerton M (2007) Histatin 5 initiates osmotic stress response in Candida albicans via activation of the Hog1 mitogen-activated protein kinase pathway. Eukaryot Cell 6(10):1876-1888.
Vylkova S, Nayyar N, Li W, Edgerton M (2007) Human beta-defensins kill Candida albicans in an energy-dependent and salt-sensitive manner without causing membrane disruption. Antimicrob Agents Chemother 51(1):154-161.
Vylkova S, Sun JN, Edgerton M (2007) The role of released ATP in killing Candida albicans and other extracellular microbial pathogens by cationic peptides. Purinergic Signal 3(1-2):91-97.
Vylkova S, Li XS, Berner JC, Edgerton M (2006) Distinct antifungal mechanisms: beta-defensins require Candida albicans Ssa1 protein, while Trk1p mediates activity of cysteine-free cationic peptides. Antimicrob Agents Chemother 50(1), 324-331.
Baev D, Rivetta A, Vylkova S, Sun JN, Zeng GF, Slayman CL, Edgerton M (2004) The TRK1 potassium transporter is the critical effector for killing of Candida albicans by the cationic protein, Histatin 5. J Biol Chem 279(53):55060-55072.
Baev D, Rivetta A, Li XS, Vylkova S, Bashi E, Slayman CL, Edgerton M (2003) Killing of Candida albicans by human salivary histatin 5 is modulated, but not determined, by the potassium channel TOK1. Infect Immun 71(6):3251-3260.
Dong J, Vylkova S, Li XS, Edgerton M (2003) Calcium blocks fungicidal activity of human salivary histatin 5 through disruption of binding with Candida albicans. J Dent Res 82(9):748-752.