Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
Mol Microbiol. 2010 Mar;75(5):1112-32. doi: 10.1111/j.1365-2958.2009.07018.x. Epub 2010 Feb 4.
Phospholipid biosynthetic pathways play crucial roles in the virulence of several pathogens; however, little is known about how phospholipid synthesis affects pathogenesis in fungi such as Candida albicans. A C. albicans phosphatidylserine (PS) synthase mutant, cho1 Delta/Delta, lacks PS, has decreased phosphatidylethanolamine (PE), and is avirulent in a mouse model of systemic candidiasis. The cho1 Delta/Delta mutant exhibits defects in cell wall integrity, mitochondrial function, filamentous growth, and is auxotrophic for ethanolamine. PS is a precursor for de novo PE biosynthesis. A psd1 Delta/Delta psd2 Delta/Delta double mutant, which lacks the PS decarboxylase enzymes that convert PS to PE in the de novo pathway, has diminished PE levels like those of the cho1 Delta/Delta mutant. The psd1 Delta/Delta psd2 Delta/Delta mutant exhibits phenotypes similar to those of the cho1 Delta/Delta mutant; however, it is slightly more virulent and has less of a cell wall defect. The virulence losses exhibited by the cho1 Delta/Delta and psd1 Delta/Delta psd2 Delta/Delta mutants appear to be related to their cell wall defects which are due to loss of de novo PE biosynthesis, but are exacerbated by loss of PS itself. Cho1p is conserved in fungi, but not mammals, so fungal PS synthase is a potential novel antifungal drug target.
磷脂生物合成途径在几种病原体的毒力中起着至关重要的作用；然而，对于磷脂合成如何影响白色念珠菌等真菌的发病机制知之甚少。白色念珠菌磷脂酰丝氨酸（PS）合酶突变体 cho1Δ/Δ 缺乏 PS，PE 减少，在系统性念珠菌病的小鼠模型中无致病性。cho1Δ/Δ 突变体表现出细胞壁完整性、线粒体功能、丝状生长缺陷，并对乙醇胺营养缺陷。PS 是从头合成 PE 的前体。psd1Δ/Δ psd2Δ/Δ 双突变体缺乏从头途径中将 PS 转化为 PE 的 PS 脱羧酶，其 PE 水平与 cho1Δ/Δ 突变体相似。psd1Δ/Δ psd2Δ/Δ 突变体表现出与 cho1Δ/Δ 突变体相似的表型；然而，它的毒力略高，细胞壁缺陷更小。cho1Δ/Δ 和 psd1Δ/Δ psd2Δ/Δ 突变体表现出的毒力丧失似乎与其细胞壁缺陷有关，这是由于从头合成 PE 减少所致，但由于 PS 本身的丧失而加剧。Cho1p 在真菌中保守，但在哺乳动物中不存在，因此真菌 PS 合酶是一种有潜力的新型抗真菌药物靶点。
