The alkene 1-dodecene (C12) and the aromatic alcohols (tryptophol and tyrosol) present in the secretome of the fungal pathogen Candida glabrata activate the oxidative stress response.

Candida glabrata is an important opportunistic fungal pathogen affecting immunocompromised individuals. Yeast cells exist in logarithmic-phase (LP) and stationary-phase (SP) states, with SP cells exhibiting high resistance to oxidative stress. Here, we show that LP cells become resistant to oxidative stress when exposed to nutritional stress and to conditioned medium from SP cells (CM, SP cell-free conditioned/spent medium). This adaptation requires the induction of CTA1 (catalase I) and the transcription factors (TFs) Yap1, Skn7, Msn2, and Msn4. In addition, CM reduces reactive oxygen species (ROS) production. Key secreted metabolites identified in the C. glabrata secretome include 1-dodecene (C12) and the aromatic alcohols (AAs) tyrosol and tryptophol. These metabolites increase H₂O₂ resistance in LP cells, but C12 induces the expression of CTA1, indicating that these are signaling molecules that confer resistance to ROS but through different pathways. C12-dependent induction of CTA1 depends on Yap1 and Skn7, while induction of CTA1 by nutrient starvation requires Msn2 and Msn4 suggesting different signal transduction pathways. RNA-seq analysis reveals that CM, C12, and AA up-regulate oxidative stress response genes, with C12 and CM inducing transcriptional profiles that resemble SP cells. This transcriptional reprogramming enhances OSR in LP cells, highlighting the role of quorum sensing molecules (QSM) in adaptive defense mechanisms of C. glabrata.