Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, New York, NY 10461, USA.
Microbes Infect. 2011 Jul;13(7):663-72. doi: 10.1016/j.micinf.2011.02.009. Epub 2011 Mar 21.
Neutral lipid storage in lipid droplets (LDs) is a conserved process across diverse species. Although significant attention has focused on LDs in the biology of obesity, diabetes, and atherosclerosis, there is limited information on the role of LDs in pathogenic fungi. We have disrupted the Fat storage-Inducing Transmembrane (FIT) protein 2 genes of the emerging pathogenic fungus Candida parapsilosis and demonstrated that LD formation is significantly reduced in the mutant cells. Disruption of FIT2 genes also reduced accumulation of triacylglycerols. The production of other lipids such as phospholipids and steryl esters were also affected in the mutant strain. Inhibition of de novo fatty acid biosynthesis by triclosan in the FIT2 disruptants reduced fungal growth in rich medium YPD, indicating that TAGs or fatty acids from the LDs could be important for cell proliferation. FIT2 disruption was associated with enhanced sensitivity to oxidative stress. Furthermore, we showed that FIT2 deletion yeast cells were significantly attenuated in murine infection models, suggesting an involvement of LDs in the pathobiology of the fungus.
中性脂质在脂滴 (LDs) 中的储存是一种在不同物种中保守的过程。尽管人们对肥胖症、糖尿病和动脉粥样硬化生物学中的 LDs 给予了极大的关注，但关于 LDs 在致病真菌中的作用的信息有限。我们已经破坏了新兴致病真菌近平滑念珠菌中的脂肪储存诱导跨膜 (FIT) 蛋白 2 基因，并证明突变细胞中 LD 的形成明显减少。FIT2 基因的破坏也减少了三酰基甘油的积累。在突变株中，其他脂质如磷脂和甾醇酯的产生也受到影响。在 FIT2 缺失突变体中，三氯生抑制从头脂肪酸生物合成，降低了富含 YPD 培养基中的真菌生长，表明 LD 中的 TAG 或脂肪酸可能对细胞增殖很重要。FIT2 缺失与氧化应激敏感性增强有关。此外，我们还表明，FIT2 缺失酵母细胞在小鼠感染模型中明显减弱，这表明 LDs 参与了真菌的病理生物学。
