van Ooij C, Kalman L, Nishijima M, Hanada K, Mostov K, Engel J N
Department of Medicine, University of California at San Francisco, 94143, USA.
Cell Microbiol. 2000 Dec;2(6):627-37. doi: 10.1046/j.1462-5822.2000.00077.x.
Chlamydia trachomatis, an important cause of human disease, is an obligate intracellular bacterial pathogen that relies on the eukaryotic host cell for its replication. Recent reports have revealed that the C. trachomatis vacuole receives host-derived sphingolipids by fusing with trans-Golgi network (TGN)derived secretory vesicles. Here, it is shown that these lipids are required for the growth of the bacteria. C. trachomatis was unable to replicate at 39 degrees C in the Chinese hamster ovary (CHO)-derived cell line SPB-1, a cell line incapable of synthesizing sphingolipids at this temperature because of a temperature-sensitive mutation in the serine palmitoyltransferase (SPT) gene. Complementation with the wild-type SPT gene or addition of exogenous cell-permeable sphingolipid precursors to the mutant cells restored their ability to support chlamydial replication. L-cycloserine (L-CS) and fumonisin B1 (FB1), inhibitors of sphingolipid biosynthesis, decreased the proliferation of the bacteria in eukaryotic cells at concentrations that also decreased host cell sphingolipid synthesis. In the case of FB1, the vacuoles appeared aberrant; the addition of sphingolipid precursors was able to reverse the altered morphology of the FB1-treated vacuoles. Collectively, these data strongly suggest that the growth and replication of chlamydiae is dependent on synthesis of sphingolipids by the eukaryotic host cell and may contribute to this organism's obligate intracellular parasitism.
沙眼衣原体是人类疾病的重要病因，是一种专性细胞内细菌病原体，其复制依赖于真核宿主细胞。最近的报道显示，沙眼衣原体空泡通过与反式高尔基体网络（TGN）衍生的分泌囊泡融合来接收宿主来源的鞘脂。在此研究中发现，这些脂质是细菌生长所必需的。沙眼衣原体在中国仓鼠卵巢（CHO）衍生的细胞系SPB-1中于39℃无法复制，该细胞系由于丝氨酸棕榈酰转移酶（SPT）基因的温度敏感突变而在此温度下无法合成鞘脂。用野生型SPT基因进行互补或向突变细胞中添加外源性细胞可渗透鞘脂前体可恢复其支持衣原体复制的能力。鞘脂生物合成抑制剂L-环丝氨酸（L-CS）和伏马菌素B1（FB1）在降低宿主细胞鞘脂合成的浓度下，降低了真核细胞中细菌的增殖。就FB1而言，空泡出现异常；添加鞘脂前体能够逆转经FB1处理的空泡的形态改变。总体而言，这些数据有力地表明，衣原体的生长和复制依赖于真核宿主细胞鞘脂的合成，这可能促成了该生物体的专性细胞内寄生现象。
