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源自人乳中化合物的新型抗菌脂质对沙眼衣原体的杀灭作用。

Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk.

作者信息

Lampe M F, Ballweber L M, Isaacs C E, Patton D L, Stamm W E

机构信息

University of Washington, Seattle 98195, USA.

出版信息

Antimicrob Agents Chemother. 1998 May;42(5):1239-44. doi: 10.1128/AAC.42.5.1239.

Abstract

The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority. Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure. To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk. C. trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times. Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted. A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C. trachomatis after 120 min of contact with the organism. The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity. On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell. Lipid activity was unaffected by the presence of 10% human blood or alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in the vagina. Our results suggest that these lipids, especially 2-O-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C. trachomatis. Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress.

摘要

开发预防性传播沙眼衣原体感染的新方法是公共卫生的首要任务。局部自我给药的阴道杀菌剂就是这样一种方法,可在初次接触病原体时将其根除。为此,我们研究了五种从人母乳中天然存在的化合物衍生而来的合成脂质的活性。将沙眼衣原体血清型D或F原体添加到脂质的系列稀释液中,并孵育不同时间。然后将等分试样接种到 McCoy 细胞单层中培养,并计数包涵体。7.5 mM浓度的2-O-辛基-sn-甘油在与病原体接触120分钟后完全抑制了沙眼衣原体的生长。其余脂质,1-O-辛基-、1-O-庚基-、2-O-己基-和1-O-己基-sn-甘油,活性较低。电子显微镜检查显示,这些脂质破坏了衣原体的内膜,使细胞质内容物从细胞中泄漏出来。脂质活性不受10%人血的存在或pH值从4.0到8.0变化的影响,这些条件反映了阴道中有时会出现的情况。我们的结果表明,这些脂质,尤其是2-O-辛基-sn-甘油,可能作为局部杀菌剂有效预防沙眼衣原体的传播。目前正在对这些脂质进行进一步的疗效和毒性研究,并评估它们对其他性传播疾病病原体的活性。

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