Host HDL biogenesis machinery is recruited to the inclusion of Chlamydia trachomatis-infected cells and regulates chlamydial growth.
Host HDL biogenesis machinery is recruited to the inclusion of Chlamydia trachomatis-infected cells and regulates chlamydial growth.
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DOI：
10.1111/j.1462-5822.2012.01823.x
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发表时间：
2012-10
影响因子：
3.4
通讯作者：
Belland RJ
中科院分区：
文献类型：
--
作者：
Cox JV;Naher N;Abdelrahman YM;Belland RJ
沙眼衣原体是一种专性细胞内细菌病原体，是性传播细菌感染的最常见原因，也是沙眼的病原体，沙眼是可预防失明的主要原因。该微生物感染生殖道和眼睑的上皮细胞，导致破坏性炎症反应。C.沙眼衣原体在称为包涵体的空泡内生长，其生长取决于包括脂质在内的许多宿主因素。虽然C.对于沙眼衣原体，先前记录的脂质获取途径中没有一个是生长绝对需要的。在这里，我们证明了宿主高密度脂蛋白（HDL）生物合成机制的多种成分，包括脂质流出物ABCA 1和CLA 1，以及它们的细胞外脂质受体apoA-1，被招募到C。沙眼感染细胞此外，在包涵体内积累的apoA-1与磷脂酰胆碱池共定位。ABCA 1介导细胞内胆固醇和磷脂流出，启动血清中HDL的形成，ABCA 1的敲低可阻止C.沙眼衣原体感染的HeLa细胞。此外，抑制ABCA 1和CLA 1的脂质转运活性的药物也抑制磷脂向包涵体的募集并防止衣原体生长。这些结果表明C.沙眼衣原体选择参与HDL形成的宿主细胞脂质转运系统，以获得生长所必需的脂质，如磷脂酰胆碱。
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that is the most common cause of sexually transmitted bacterial infections and is the etiological agent of trachoma, the leading cause of preventable blindness. The organism infects epithelial cells of the genital tract and eyelid resulting in a damaging inflammatory response. C. trachomatis grows within a vacuole termed the inclusion, and its growth depends on numerous host factors, including lipids. Although a variety of mechanisms are involved in the acquisition of host cell cholesterol and glycosphingolipids by C. trachomatis, none of the previously documented pathways for lipid acquisition are absolutely required for growth. Here we demonstrate that multiple components of the host high density lipoprotein (HDL) biogenesis machinery including the lipid effluxers, ABCA1 and CLA 1, and their extracellular lipid acceptor, apoA-1, are recruited to the inclusion of C. trachomatis-infected cells. Furthermore, the apoA-1 that accumulates within the inclusion co-localizes with pools of phosphatidylcholine. Knockdown of ABCA1, which mediates the cellular efflux of cholesterol and phospholipids to initiate the formation of HDL in the serum, prevents the growth of C. trachomatis in infected HeLa cells. In addition, drugs that inhibit the lipid transport activities of ABCA1 and CLA 1 also inhibit the recruitment of phospholipids to the inclusion and prevent chlamydial growth. These results strongly suggest that C. trachomatis co-opts the host cell lipid transport system involved in the formation of HDL to acquire lipids, such as phosphatidylcholine, that are necessary for growth.
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DOI：
10.1073/pnas.88.7.2793
发表时间：
1991-04-01
影响因子：
11.1
作者：
MATSUNAGA, T;HIASA, Y;HAMAGUCHI, H
通讯作者：
HAMAGUCHI, H
DOI：
10.1038/nrm2937
发表时间：
2010-08
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.7
作者：
Derré I;Swiss R;Agaisse H
通讯作者：
Agaisse H
影响因子：
4.8
作者：
Arakawa, R;Yokoyama, S
通讯作者：
Yokoyama, S
DOI：
10.1073/pnas.92.11.4877
发表时间：
1995-05-23
影响因子：
11.1
作者：
HACKSTADT, T;SCIDMORE, MA;ROCKEY, DD
通讯作者：
ROCKEY, DD