ANTIMICROBIAL ACTIVITIES OF CLOFAZIMINE AND B669 ARE MEDIATED BY LYSOPHOSPHOLIPIDS
ANTIMICROBIAL ACTIVITIES OF CLOFAZIMINE AND B669 ARE MEDIATED BY LYSOPHOSPHOLIPIDS
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DOI：
10.1128/aac.36.12.2729
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发表时间：
1992-12-01
影响因子：
4.9
通讯作者：
ANDERSON, R
中科院分区：
文献类型：
--
作者：
VANRENSBURG, CEJ;JOONE, GK;ANDERSON, R
研究了一系列革兰氏阳性和革兰氏阴性微生物病原体对氯法齐明及其类似物B669（0.1 ~ 32马克杯/毫升）的敏感性，以及这些药物对金黄色葡萄球菌和大肠杆菌膜磷脂代谢的影响。革兰氏阳性细菌一般对这些药物敏感，而革兰氏阴性细菌则一致耐药。金黄色葡萄球菌暴露于这两种药物（1至5马克杯/毫升），特别是B669，根据从细菌膜磷脂中释放的H-3放射性标记的花生四烯酸酯和溶血磷脂酰乙醇胺（[H-3]LPE）的增加，引起磷脂酶A2活性的剂量相关增强。用丙胺非那嗪处理大肠杆菌也增加了[H-3]花生四烯酸酯和[H-3]LPE的释放。LPE和溶血磷脂酰胆碱对革兰氏阳性菌和革兰氏阴性菌的生长均有抑制作用。此外，与α -生育酚（维生素E），溶血磷脂复合物形成剂，或与溶血磷脂酶共孵育保护革兰氏阳性细菌免受胺苯那嗪和溶血磷脂的侵害。这项研究的结果与溶血磷脂介导两种药物活性的机制是一致的。
The susceptibilities of a range of gram-positive and gram-negative microbial pathogens to clofazimine and its analog B669 (0.1 to 32 mug/ml), as well as the effects of these agents on membrane phospholipid metabolism in Staphylococcus aureus and Escherichia coli, have been investigated in vitro. Gram-positive bacteria were found to be generally susceptible to these agents, whereas gram-negative organisms were uniformly resistant. Exposure of S. aureus to both agents (I to 5 mug/ml), especially B669, caused dose-related enhancement of the activity of phospholipase A2, according to an increase in the release of H-3-radiolabeled arachidonate and lysophosphatidylethanolamine ([H-3]LPE) from bacterial-membrane phospholipids. Treatment of E. coli with the riminophenazines also increased the release of [H-3]arachidonate and [H-3]LPE. Growth of gram-positive but not gram-negative bacteria was inhibited by LPE and lysophosphatidylcholine. Moreover, coincubation with alpha-tocopherol (vitamin E), a lysophospholipid complex-forming agent, or with lysophospholipase protected gram-positive bacteria against the riminophenazines as well as against lysophospholipids. The results from this study are consistent with a mechanism whereby lysophospholipids mediate the activities of the two drugs.