Genes required for glycolipid synthesis and lipoteichoic acid anchoring in Staphylococcus aureus
Genes required for glycolipid synthesis and lipoteichoic acid anchoring in Staphylococcus aureus
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DOI：
10.1128/jb.01683-06
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发表时间：
2007-03-01
影响因子：
3.2
通讯作者：
Schneewind, Olaf
中科院分区：
文献类型：
--
作者：
Grundling, Angelika;Schneewind, Olaf
金黄色葡萄球菌脂磷壁酸（LTA）由线性1，3-连接的聚甘油磷酸链组成，并通过糖脂（二葡糖基-二酰基甘油[Glc（2）-DAG]）与细菌膜相连。Glc（2）-DAG在细菌细胞质中由YpfP合成，YpfP是一种使用UDP-葡萄糖作为其底物将葡萄糖转化为二酰基甘油（DAG）的加工酶。在这里，我们提出的证据表明，S。金黄色葡萄球菌α-磷酸葡萄糖变位酶（PgcA）和UTP：α-葡萄糖1-磷酸尿苷基转移酶（GtaB）同系物是合成Glc（2）-DAG所必需的。LtaA（脂磷壁酸蛋白A）是一种预测的膜通透酶，其结构基因位于具有ypfP的操纵子中，不参与Glc（2）-DAG合成，但为糖脂锚定的LTA合成所需。我们的数据表明了一种模型，其中LtaA促进Glc（2）-DAG从质膜的内（细胞质）小叶转运到外小叶，递送Glc（2）-DAG作为LTA合成的底物，从而产生糖脂锚定的LTA。LTA的糖脂锚定似乎在感染过程中起重要作用，如S。缺乏ltaA的金黄色葡萄球菌变体在动物感染的发病机理中显示缺陷。
Staphylococcus aureus lipoteichoic acid (LTA) is composed of a linear 1,3-linked polyglycerolphosphate chain and is tethered to the bacterial membrane by a glycolipid (diglucosyl-diacylglycerol [Glc(2)-DAG]). Glc(2)-DAG is synthesized in the bacterial cytoplasm by YpfP, a processive enzyme that transfers glucose to diacylglycerol (DAG), using UDP-glucose as its substrate. Here we present evidence that the S. aureus alpha-phosphoglucomutase (PgcA) and UTP:alpha-glucose 1-phosphate uridyltransferase (GtaB) homologs are required for the synthesis of Glc(2)-DAG. LtaA (lipoteichoic acid protein A), a predicted membrane permease whose structural gene is located in an operon with ypfP, is not involved in Glc(2)-DAG synthesis but is required for synthesis of glycolipid-anchored LTA. Our data suggest a model in which LtaA facilitates the transport of Glc(2)-DAG from the inner (cytoplasmic) leaflet to the outer leaflet of the plasma membrane, delivering Glc(2)-DAG as a substrate for LTA synthesis, thereby generating glycolipid-anchored LTA. Glycolipid anchoring of LTA appears to play an important role during infection, as S. aureus variants lacking ltaA display defects in the pathogenesis of animal infections.