Candida albicans fatty acyl-CoA synthetase, CaFaa4p, is involved in the uptake of exogenous long-chain fatty acids and cell activity in the biofilm
Candida albicans fatty acyl-CoA synthetase, CaFaa4p, is involved in the uptake of exogenous long-chain fatty acids and cell activity in the biofilm
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DOI：
10.1007/s00294-017-0751-2
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发表时间：
2017-09
期刊：
影响因子：
2.5
通讯作者：
Kengo Tejima;Masanori Ishiai;S. Murayama;Shun Iwatani;S. Kajiwara
中科院分区：
文献类型：
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作者：
Kengo Tejima;Masanori Ishiai;S. Murayama;Shun Iwatani;S. Kajiwara
脂肪酰基辅酶A合成酶（Faa）通过在细胞中将脂肪酸（FA）转化为辅酶A酯来活化FA。在本研究中，我们的特点aFAA同源物（CaFAA 4）的机会致病菌白色念珠菌。大多数生物体不仅可以利用脂肪酸合成酶（Fas）活性内源性合成长链脂肪酰辅酶A（LCFA-CoA），而且可以从细胞外环境摄取长链脂肪酸（LCFA）并通过载体酰化系统将其转化为LCFA-CoA。芽殖酵母Saccharomycesae具有两种LCFA-CoA合成酶ScFaa1p和ScFaa4p。ScFAA 1和ScFAA 4的破坏导致在脂肪酸合成途径浅蓝菌素存在下的合成致死性。同源物CaFAA4挽救了anS的致死性。酿酒酵母Scfaa1-Scfa4双突变体在浅蓝菌素存在下的表达。另一方面，aC。白色念珠菌faa4突变体不能在浅蓝菌素存在下生长，即使外源提供LCFA。此外，生物膜分析表明，theCafaa4突变体的代谢活性比野生型亲本低约40%，即使这些菌株之间的细胞数量或细胞形态没有显着差异。值得注意的是，Cafaa4突变体在生物膜形成过程中对米卡芬净的敏感性增加，这种表型可能归因于突变菌株的代谢受损。这些结果表明CaFaa4p是唯一的C. albicansFaa蛋白负责激活LCFA并参与生物膜的代谢。
Fatty acyl-CoA synthetase (Faa) activates fatty acid (FA) by converting the FA into the CoA ester in the cell. In the present study, we characterized aFAAhomologue (CaFAA4) from the opportunistic pathogenCandida albicans. Most organisms can not only synthesize long-chain fatty acyl-CoAs (LCFA-CoAs) endogenously using a fatty acid synthase (Fas) activity but also can uptake long-chain fatty acids (LCFAs) from the extracellular environment and convert them into LCFA-CoAs via a vectorial acylation system. The budding yeastSaccharomyces cerevisiaepossesses two LCFA-CoA synthetases,ScFaa1p andScFaa4p. The disruption ofScFAA1andScFAA4leads to synthetic lethality in the presence of a fatty acid synthesis inhibitor—cerulenin. The homologue—CaFAA4—rescued the lethality of anS. cerevisiae Scfaa1–Scfaa4double mutant in the presence of cerulenin. On the other hand, aC. albicans faa4mutant was unable to grow in the presence of cerulenin even if LCFAs were provided exogenously. Moreover, a biofilm analysis showed that the metabolic activity of theCafaa4mutant was approximately 40% lower than that of the wild-type parent, even though there was no significant difference in cell number or cell morphology between these strains. Notably, theCafaa4mutant showed increased susceptibility to micafungin during biofilm formation, a phenotype that presumably can be attributed to the impaired metabolism of the mutant strain. These results indicated thatCaFaa4p is the uniqueC. albicansFaa protein responsible for activating LCFAs and is involved in the metabolism of biofilms.