Until 2022

C. albicans is an opportunistic pathogen. The fungus can turn from a harmless colonizer into a pathogen, causing a range of infections: from mild superficial infections of mucosal surfaces and skin to severe disseminated candidiasis.
C. albicans is an opportunistic pathogen. The fungus can turn from a harmless colonizer into a pathogen, causing a range of infections: from mild superficial infections of mucosal surfaces and skin to severe disseminated candidiasis.

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. Importantly, the tight association with humans, both as a commensal and a pathogen, has driven the evolution of mechanisms that permit rapid metabolic adaptations to the changing environments within the host, where the availability of nutrients is often limited. Previous work by our lab and others shows in fact that such metabolic plasticity plays an important role in pathogenicity. Therefore, we investigate the mechanistic links that connect metabolic adaptations and alterations to the commensal-to-pathogen shift, stress resistance, expression of virulence determinants, and drug susceptibility.


Slavena Vylkova

Interconnection between metabolic signals and virulence networks

Adequate nutrition is a fundamental prerequisite for C. albicans persistence in the human host. The adaptation to and proliferation in nutrient-restrictive host niches is not only critical for survival, but also for the ability of the fungus to cause infection. Thus, C. albicans has evolved remarkable metabolic plasticity, such as the ability to utilize simultaneously preferred and non-preferred carbon sources or quickly switch from growth on one nutrient to another.  We are particularly interested in i) molecular mechanisms of metabolic adaptation of C. albicans and ii) the metabolic changes that accompany the transition from a commensal to a pathogen.


Candida albicans has evolved to rapidly sense, acquire and metabolize various host nutrients. Sensing of extracellular nutrients frequently triggers signaling cascades, intercepted with virulence networks, which ultimately leads to invasive growth and infection.
Figure from Alves et al., PLoS Pathogens 2020

Niche-specific metabolic adaptations of Candida albicans

Candida albicans cells rapidly tune their metabolism to the ever changing nutrient conditions of the diverse and complex host microenvironments. Thus, the expression of key metabolic functions is niche-specific. C. albicans cells induce glycolytic, tricarboxylic acid cycle, and fatty acid β-oxidation genes during mucosal invasion, whereas in the bloodstream and during biofilm growth C. albicans populations are heterogeneous, with metabolic signatures of their immediate microenvironments or stage of aging. The metabolic characteristics of a single host niche likely change during infection: a state typically triggered by severe alterations in the associated protective microbiota or in individuals with immune deficiencies. The nature of such changes is yet to be discovered. Therefore we aim to understand i) the niche-specific metabolic fingerprints and ii) alterations in C. albicans metabolic exchanges between the host and associated microbiota that trigger the infection process

C. albicans has adapted to thrive in various host niches, each with different nutrient repertoire. We study the metabolic processes that accompany commensalism and infection using selected models of host-fungal interactions.

Candida albicans-unique metabolic features

Phylogeny of sequenced Candida and Saccharomyces clade species. Figure from Butler et al., Nature 2009
Phylogeny of sequenced Candida and Saccharomyces clade species.
Figure from Butler et al., Nature 2009

Candida albicans is the most common cause of mucosal and systemic candidiasis. Other related Candida species, such as Candida glabrata, Candida parapsilosis, Candida tropicalis and the emerging pathogen Candida auris have also been associated with most forms of candidiasis, though far less frequently. C. albicans is very closely related to Candida dubliniensis, with which it shares many phenotypic properties, including the ability to produce hyphae, an important pathogenicity trait. Surprisingly, despite the close phylogenetic relationship of the two species epidemiological data show that C. albicans is far more prevalently associated with the host than C. dubliniensis. Certain features, such as differences in posttranslational regulation of hyphal growth distinguish the two species. Interestingly, C. dubliniensis seems to lack the metabolic flexibility of C. albicans, but the reasons for this remain unexplored. We argue that C. albicans possess specific metabolic features lacking in the closely related C. dubliniensis and C. africana that make it both a successful colonizer and a pathogen.



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 Spectr 11(3), e0049823.
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 11(2), e0025323.
Rebai Y, Wagner L, Gnaien M, Hammer ML, Kapitan M, Niemiec MJ, Mami W, Mosbah A, Messadi E, Mardassi H, 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(8), 1929.
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.
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.
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, Gerwien F, Driesch D, Müller T, Böttcher B, Gräler M, Vylkova S (2022) Systematic metabolic profiling identifies de novo sphingolipid synthesis as hypha associated and essential for Candida albicans filamentation. mSystems 7(6), e0053922.
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.
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.
Roth M, Holtmann C, Daas L, Kakkassery V, Kurzai O, Geerling G, Bäurle S, Bayoudh W, Brücher V, Cvetkova-Fischer N, Dias Blak M, Bornstein A, Fischer C, Fuest M, Grisanti S, Herwig-Carl M, Kroll S, Lenk J, Lommatzsch C, MacKenzie C, Matthaei M, Mehlan J, Messmer E, Müller V, Pawlik V, Ranjbar M, Renner-Wilde A, Rickmann A, Saeger M, Schargus M, Schwarz L, Seitz B, Steindor F, Unterlauf JD, Viestenz A, von Lilienfeld-Toal M, Walther G (2021) Results from the German fungal keratitis registry: Significant differences between cases with and without a history of contact lens use. Cornea 40(11), 1453-1461.