Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium tuberculosis.

Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium tuberculosis.
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DOI:
10.1016/j.tube.2013.12.005
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发表时间:
2014-03
期刊:
Tuberculosis (Edinburgh, Scotland)
影响因子:
--
通讯作者:
Bigi F
Bigi F
中科院分区:
其他
文献类型:
--
作者:
Forrellad MA;McNeil M;Santangelo Mde L;Blanco FC;García E;Klepp LI;Huff J;Niederweis M;Jackson M;Bigi F

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结核病是全世界导致死亡的主要原因之一。结核分枝杆菌是人类结核病的病原体,它已经开发出几种策略,涉及蛋白质和其他化合物,统称为毒力因子,以颠覆人类宿主防御系统,入侵人类宿主。MCE蛋白是这些毒力相关蛋白之一,由结核分枝杆菌基因组中的mce1、mce2、mce3和mce4操纵子编码。有人提出这些操纵子编码ABC样脂转运蛋白;然而,它们底物的性质只在Mce4蛋白的情况下才被揭示。在这里,我们发现mce1操纵子的敲除改变了结核分枝杆菌H37Rv的脂谱和对棕榈酸的摄取。薄层层析和液质联用分析表明,mce1突变株比野生型和补充型菌株积累了更多的真菌酸。有趣的是,当细菌在棕榈酸或花生四烯酸存在的情况下培养时,这种真菌酸的积累会加剧。这些结果表明,mce1操纵子可能作为霉菌酸再输入载体。
Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the causative agent of human tuberculosis, has developed several strategies involving proteins and other compounds known collectively as virulence factors to subvert human host defences and invade the human host. The Mce proteins are among these virulence-related proteins and are encoded by the mce1, mce2, mce3 and mce4 operons in the genome of M. tuberculosis. It has been proposed that these operons encode ABC-like lipid transporters; however, the nature of their substrates has only been revealed in the case of the Mce4 proteins. Here we found that the knockout of the mce1 operon alters the lipid profile of M. tuberculosis H37Rv and the uptake of palmitic acid. Thin layer chromatography and liquid chromatography-mass spectrometry analysis showed that the mce1 mutant accumulates more mycolic acids than the wild type and complemented strains. Interestingly, this accumulation of mycolic acid is exacerbated when bacteria are cultured in the presence of palmitic acid or arachidonic acid. These results suggest that the mce1 operon may serve as a mycolic acid re-importer.
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