Regulation of primary metabolism and hyphal morphogenesis in Candida albicans

We monitor energy flow and metabolic inputs and outputs from biofilm cells and planktonic cultures under physiologically relevant conditions.

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 the utilization of amino acids, which serve both as a nitrogen and as a carbon source in C. albicans, since their metabolism triggers hyphal morphogenesis – a key virulence factor.

In this context, we assess transcriptional (via RNASeq) and metabolic changes (via Metabolomics & Secretomics) in relation to each other to gain insight into the cellular metabolism and the associated pathogenicity traits (e.g. biofilm formation).

Furthermore, large-scale screening using phenotypic microarrays enables us to generate metabolic profiles of microorganisms.  By applying this approach to C. albicans deletion mutants it can help us elucidate the relationship between genome and cellular metabolism.

C. albicans cells can metabolize host-derived amino acids both as a carbon and as a nitrogen source. When used as a carbon source, excess NH3 is released from the cell, resulting in prominent neutralization the environmental pH. Utilization of extracellular amino acids also drives hyphal morphogenesis, a well-recognized virulence factor, in a process tightly controlled by the transcription factor Stp2.