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PP2A-like phosphatases share high homology with PP2A enzymes and are composed of a catalytic subunit and a regulatory subunit. In  Candida albicans , the PP2A-like catalytic subunit  SIT4  regulates cell growth, morphogenesis, and virulence. However, the functions of its regulatory subunits remain unclear. Here, by homology analysis and co-IP experiments, we identified two regulatory subunits of  SIT4  in  C. albicans ,  SAP155  (orf19.642) and  SAP190  (orf19.5160). We constructed  sit4 Δ/Δ,  sap155 Δ/Δ,  sap190 Δ/Δ, and  sap155 Δ/Δ  sap190 Δ/Δ mutants and found that deleting  SAP155  had no apparent phenotypic consequence, while deleting  SAP190  caused slow growth, hypersensitivity to cell wall stress, abnormal morphogenesis in response to serum or genotoxic stress (HU and MMS), less damage to macrophages, and attenuated virulence in mice. However, deleting both  SAP155  and  SAP190  caused significantly stronger defects, which was similar to deleting  SIT4 . Together, our results suggest that  SAP190  is required for the function of  SIT4  and that  SAP155  can partially compensate for the loss of  SAP190  in  C. albicans . Given the vital role of these regulatory subunits of  SIT4  in  C. albicans  physiology and virulence, they could serve as potential antifungal targets.

PP2A-Like Protein Phosphatase (Sit4) Regulatory Subunits, Sap155 and Sap190, Regulate Candida albicans’ Cell Growth, Morphogenesis, and Virulence