AUTHOR=Han Qi , Pan Chaoying , Wang Yueqing , Zhao Linpeng , Wang Yue , Sang Jianli 

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

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02943

DOI=10.3389/fmicb.2019.02943

ISSN=1664-302X

ABSTRACT=<p>PP2A-like phosphatases share high homology with PP2A enzymes and are composed of a catalytic subunit and a regulatory subunit. In <italic>Candida albicans</italic>, the PP2A-like catalytic subunit <italic>SIT4</italic> 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 <italic>SIT4</italic> in <italic>C. albicans</italic>, <italic>SAP155</italic> (orf19.642) and <italic>SAP190</italic> (orf19.5160). We constructed <italic>sit4</italic>Δ/Δ, <italic>sap155</italic>Δ/Δ, <italic>sap190</italic>Δ/Δ, and <italic>sap155</italic>Δ/Δ <italic>sap190</italic>Δ/Δ mutants and found that deleting <italic>SAP155</italic> had no apparent phenotypic consequence, while deleting <italic>SAP190</italic> 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 <italic>SAP155</italic> and <italic>SAP190</italic> caused significantly stronger defects, which was similar to deleting <italic>SIT4</italic>. Together, our results suggest that <italic>SAP190</italic> is required for the function of <italic>SIT4</italic> and that <italic>SAP155</italic> can partially compensate for the loss of <italic>SAP190</italic> in <italic>C. albicans</italic>. Given the vital role of these regulatory subunits of <italic>SIT4</italic> in <italic>C. albicans</italic> physiology and virulence, they could serve as potential antifungal targets.</p>