Fungal proteomic response to PFAS mixtures: Defense or offense?

The differential expression of molecular markers identified in response to environmental contaminants offer insights into early-stage resilience pathways that may support biological remediation approaches. Per- and polyfluoroalkyl substances (PFAS) are chemically stable, persistent environmental pollutants, which are associated with multiple adverse health effects. While fungi possess oxidative enzymes with potential for PFAS biotransformation, the molecular basis of their tolerance and response remains poorly understood. This study investigated the proteomic response of Phanerochaete chrysosporium to 10 mg/L PFOA and an environmentally relevant concentration of a PFAS mixture. Although no measurable PFAS degradation was observed over a 25-day exposure period, significant differential protein expression of key stress-response proteins such as cytochrome P450s, glutathione S-transferases, heat shock proteins, peroxidases, and ABC transporters were noted, in both intra- and extracellular fractions. Functional enrichment revealed the activation of pathways related to posttranslational modification, protein turnover, membrane efflux mechanisms, catabolism, and signal transduction. Proteomic profiles were shaped more closely by exposure duration and localization than by compound identity. These findings highlight the early-stage adaptations and signaling mechanisms of wood-decaying fungi under PFAS stress, which precede observable chemical breakdown and offer critical insights into fungal responses that may be leveraged for future monitoring and bioremediation strategies. • Phanerochaete chrysosporium fungus was exposed to PFOA and a complex PFAS mixture • Strong proteomic response observed despite no measurable PFAS removal in 25 days • Time- and compartment-specific protein expression showed fungal stress adaptations • Detoxification proteins (P450s, GSTs, HSPs, transporters) differentially expressed • Candidate fungal biomarkers for environmental contaminant stress were identified