Host cell phospholipids are trafficked to and then modified by Chlamydia trachomatis

Host cell phospholipids are trafficked to and then modified by Chlamydia trachomatis
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DOI:
10.1128/jb.179.23.7233-7242.1997
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发表时间:
1997-12-01
影响因子:
3.2
通讯作者:
McClarty, G
McClarty, G
中科院分区:
生物学3区
文献类型:
--
作者:
Wylie, JL;Hatch, GM;McClarty, G

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关于真核生物脂质从宿主细胞运输到细胞内病原体的细胞质膜或液泡膜的信息很少。纯化的沙眼衣原体是一种专性细胞内细菌寄生虫,含有几种真核甘油磷脂,但试图证明这些脂质转移到衣原体细胞膜尚未成功。在本报告中,我们证明真核生物甘油磷脂从宿主细胞运输到沙眼衣原体。磷脂运输是通过监测放射性标记异亮氨酸(沙眼衣原体特异性支链脂肪酸的前体)进入宿主衍生的甘油磷脂的结合,以及监测宿主磷脂酰丝氨酸向衣原体的转移及其随后的脱羧形成磷脂酰乙醇胺来评估的。磷脂运输到衣原体不受布雷菲尔丁A,高尔基功能抑制剂的影响。此外,当沙眼衣原体在具有无功能、非特异性磷脂转移蛋白的突变细胞系中生长时,运输没有变化。宿主甘油磷脂被沙眼衣原体修饰,使宿主合成的直链脂肪酸被衣原体合成的支链脂肪酸所取代。我们还证明,尽管获得宿主来源的磷脂,沙眼衣原体能够从头合成通常由原核细胞合成的磷脂。我们的研究结果为衣原体磷脂代谢和真核细胞脂质运输提供了新的信息,并增加了我们对导致在专性细胞内细菌寄生虫和真核宿主细胞之间建立密切代谢关联的进化步骤的理解。
There is little information on the trafficking of eukaryotic lipids from a host cell to either the cytoplasmic membrane of or the vacuolar membrane surrounding intracellular pathogens. Purified Chlamydia trachomatis, an obligate intracellular bacterial parasite, contains several eukaryotic glycerophospholipids, yet attempts to demonstrate transfer of these lipids to the chlamydial cell membrane have not been successful. In this report, we demonstrate that eukaryotic glycerophospholipids are trafficked from the host cell to C. trachomatis. Phospholipid trafficking was assessed by monitoring the incorporation of radiolabelled isoleucine, a precursor of C. trachomatis specific branched-chain fatty acids, into host-derived glycerophospholipids and by monitoring the transfer of host phosphatidylserine to chlamydiae and its subsequent decarboxylation to form phosphatidylethanolamine. Phospholipid trafficking to chlamydiae was unaffected by brefeldin A, an inhibitor of Golgi function. Furthermore, no changes in trafficking were observed when C. trachomatis was grown in a mutant cell line with a nonfunctional, nonspecific phospholipid transfer protein. Host glycerophospholipids are modified by C. trachomatis, such that a host-synthesized straight-chain fatty acid is replaced with a chlamydia-synthesized branched-chain fatty acid. We also demonstrate that despite the acquisition of host-derived phospholipids, C. trachomatis is capable of de novo synthesis of phospholipids typically synthesized by prokaryotic cells. Our results provide novel information on chlamydial phospholipid metabolism and eukaryotic cell lipid trafficking, and they increase our understanding of the evolutionary steps leading to the establishment of an intimate metabolic association between an obligate intracellular bacterial parasite and a eukaryotic host cell.