Lundemose A G, Kay J E, Pearce J H
Microbial Molecular Genetics, University of Birmingham, UK.
Mol Microbiol. 1993 Mar;7(5):777-83. doi: 10.1111/j.1365-2958.1993.tb01168.x.
The Mip-like protein of Chlamydia trachomatis has sequence similarity with both the Mip protein of Legionella pneumophila, a virulence factor necessary for optimal intracellular infection, and FK506-binding proteins (FKBPs) of both prokaryotic and eukaryotic origin. FKBPs contain a site for peptidyl-prolyl cis/trans isomerase activity, which is blocked upon binding of the drugs, FK506 or rapamycin. In this paper we report that the recombinant chlamydial Mip-like protein exhibits a peptidyl-prolyl cis/trans isomerase activity which is inhibited by either rapamycin or FK506. To assess the role of the Mip-like protein in chlamydial infection, rapamycin or FK506 (25 microM), were used in either treatment of chlamydial organisms prior to inoculation, or were present at different intervals through the infection. Pretreatment of organisms alone reduced infectivity for McCoy cells by 30%, with inhibition rising to 80% on more prolonged exposure from 0 to 8h and 8 to 16h post-inoculation and declining thereafter. When drug was present during the developmental cycle at intervals from 0 to 24h post-inoculation abnormal chlamydiae were induced in residual inclusions. The results suggest that inhibition of the isomerase of the Mip-like protein interferes with one or more early events in the infective process that determine productive intracellular infection.
沙眼衣原体的Mip样蛋白与嗜肺军团菌的Mip蛋白（最佳细胞内感染所必需的一种毒力因子）以及原核和真核来源的FK506结合蛋白（FKBPs）均具有序列相似性。FKBPs含有一个肽基脯氨酰顺/反异构酶活性位点，该位点在药物FK506或雷帕霉素结合后会被阻断。在本文中，我们报道重组沙眼衣原体Mip样蛋白表现出一种肽基脯氨酰顺/反异构酶活性，该活性可被雷帕霉素或FK506抑制。为了评估Mip样蛋白在衣原体感染中的作用，在接种前用雷帕霉素或FK506（25 microM）处理衣原体生物体，或者在感染过程中的不同时间间隔加入这两种药物。单独对生物体进行预处理会使对McCoy细胞的感染性降低30%，随着接种后0至8小时以及8至16小时更长时间的暴露，抑制率上升至80%，此后下降。当在接种后0至24小时的发育周期中每隔一段时间加入药物时，在残留包涵体中会诱导出异常衣原体。结果表明，抑制Mip样蛋白的异构酶会干扰感染过程中决定有效细胞内感染的一个或多个早期事件。
