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.