Carnitine-dependent transport of acetyl coenzyme A in Candida albicans is essential for growth on nonfermentable carbon sources and contributes to biofilm formation
Carnitine-dependent transport of acetyl coenzyme A in Candida albicans is essential for growth on nonfermentable carbon sources and contributes to biofilm formation
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DOI：
10.1128/ec.00017-08
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发表时间：
2008-04-01
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影响因子：
--
通讯作者：
Distel, Ben
中科院分区：
文献类型：
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作者：
Strijbis, Karin;van Roermund, Carlo W. T.;Distel, Ben
在真核生物中，过氧化物酶体脂肪酸β-氧化过程中产生的乙酰辅酶A（乙酰辅酶A）需要转运到线粒体进行进一步代谢。已经在酿酒酵母中鉴定了两种平行的乙酰辅酶A转运途径;一种依赖于过氧化物酶体柠檬酸合酶（Cit），而另一种需要过氧化物酶体和线粒体肉毒碱乙酰转移酶（Cat）活性。在这里，我们表明，人类真菌病原体白色念珠菌缺乏过氧化物酶体Cit，完全依赖于猫活动的乙酰基单位的运输。缺失C.白色念珠菌导致菌株失去过氧化物酶体和与过氧化物酶体相关的Cat活性，不能在脂肪酸或C-2碳源（乙酸盐或乙醇）上生长，积累细胞内乙酰辅酶A，并显示出大大降低的脂肪酸β-氧化活性。然而，cat 2无效突变体在小鼠系统性念珠菌病模型中的毒力没有减弱。这些观察结果支持了我们先前的结果，即过氧化物酶体脂肪酸β-氧化活性对于C.白色念珠菌毒力与野生型相比，cat 2突变体在葡萄糖上的生物膜形成略有减少，尽管两种菌株在这种碳源上以相同的速率生长。我们的数据表明C. albicans与S.酿酒酵母细胞内乙酰辅酶A的运输机制，并暗示肉毒碱依赖可能是一个重要的特点，这种人类真菌病原体。
In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid beta-oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae; one is dependent on peroxisomal citrate synthase (Cit), while the other requires peroxisomal and mitochondrial carnitine acetyltransferase (Cat) activities. Here we show that the human fungal pathogen Candida albicans lacks peroxisomal Cit, relying exclusively on Cat activity for transport of acetyl units. Deletion of the CAT2 gene encoding the major Cat enzyme in C. albicans resulted in a strain that had lost both peroxisomal and mitochondrion-associated Cat activities, could not grow on fatty acids or C-2 carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA, and showed greatly reduced fatty acid beta-oxidation activity. The cat2 null mutant was, however, not attenuated in virulence in a mouse model of systemic candidiasis. These observations support our previous results showing that peroxisomal fatty acid beta-oxidation activity is not essential for C. albicans virulence. Biofilm formation by the cat2 mutant on glucose was slightly reduced compared to that by the wild type, although both strains grew at the same rate on this carbon source. Our data show that C. albicans has diverged considerably from S. cerevisiae with respect to the mechanism of intracellular acetyl-CoA transport and imply that carnitine dependence may be an important trait of this human fungal pathogen.