The PP2A Catalytic Subunit PPH21 Regulates Biofilm Formation and Drug Resistance of Candida albicans

<i>Candida albicans</i> (<i>C. albicans</i>) biofilms exhibit enhanced resistance to conventional antifungal agents; however, the underlying pathogenic mechanisms warrant deeper exploration. Protein phosphatase 2A (PP2A), especially its catalytic activity, is crucial for maintaining physiological balance. This study focused on the role of the PP2A catalytic subunit coding gene <i>PPH21</i> in biofilm formation and drug resistance of <i>C. albicans</i>. The mutant strain (<i>pph21</i>Δ/Δ) was generated and identified. The oxidative stress was detected by the reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). The autophagic activity was evaluated, and the autophagosomes were observed by transmission electron microscopy (TEM). The biofilm formation was measured by XTT reduction assay, crystal violet (CV) staining, and scanning electron microscopy (SEM). The susceptibility to antifungal agents was examined by XTT reduction assay and spot assay. Additionally, the antioxidant N-acetylcysteine (NAC) was applied to clarify the regulatory effect of <i>C. albicans</i> autophagy on oxidative stress. The pathogenicity of <i>PPH21</i> in oral <i>C. albicans</i> infection was evaluated through in vivo experiments. We found that <i>PPH21</i> deletion led to increased oxidative stress and autophagic activities, but it can be reversed by the application of NAC. Moreover, <i>PPH21</i> deletion also impaired the biofilm formation ability and reduced resistance to antifungal agents. Our findings revealed that <i>PPH21</i> is involved in both virulence and stress adaptation of <i>C. albicans</i>.