Han Qi, Pan Chaoying, Wang Yueqing, Zhao Linpeng, Wang Yue, Sang Jianli
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
Front Microbiol. 2019 Dec 20;10:2943. doi: 10.3389/fmicb.2019.02943. eCollection 2019.
PP2A-like phosphatases share high homology with PP2A enzymes and are composed of a catalytic subunit and a regulatory subunit. In , the PP2A-like catalytic subunit 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 in , (orf19.642) and (orf19.5160). We constructed Δ/Δ, Δ/Δ, Δ/Δ, and Δ/Δ Δ/Δ mutants and found that deleting had no apparent phenotypic consequence, while deleting 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 and caused significantly stronger defects, which was similar to deleting . Together, our results suggest that is required for the function of and that can partially compensate for the loss of in . Given the vital role of these regulatory subunits of in physiology and virulence, they could serve as potential antifungal targets.
PP2A样磷酸酶与PP2A酶具有高度同源性，由一个催化亚基和一个调节亚基组成。在[具体物种名称未给出]中，PP2A样催化亚基调节细胞生长、形态发生和毒力。然而，其调节亚基的功能仍不清楚。在这里，通过同源性分析和免疫共沉淀实验，我们在[具体物种名称未给出]中鉴定出了PP2A样磷酸酶的两个调节亚基，即基因名称1和基因名称2。我们构建了Δ/Δ、Δ/Δ、Δ/Δ和Δ/Δ Δ/Δ突变体，发现缺失[基因名称1]没有明显的表型后果，而缺失[基因名称2]导致生长缓慢、对细胞壁应激超敏、对血清或基因毒性应激（HU和MMS）反应时形态发生异常、对巨噬细胞的损伤较小以及在小鼠中的毒力减弱。然而，同时缺失[基因名称1]和[基因名称2]会导致明显更强的缺陷，这与缺失[另一个相关基因名称]相似。总之，我们的结果表明[基因名称2]是[PP2A样磷酸酶]功能所必需的，并且[基因名称1]可以部分补偿[PP2A样磷酸酶]中[基因名称2]的缺失。鉴于这些[PP2A样磷酸酶]调节亚基在[具体物种名称未给出]生理学和毒力中的重要作用，它们可作为潜在的抗真菌靶点。
