In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity
In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity
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DOI：
10.1128/iai.68.6.3548-3553.2000
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发表时间：
2000-06-01
影响因子：
3.1
通讯作者：
Yeaman, MR
中科院分区：
文献类型：
--
作者：
Bayer, AS;Prasad, R;Yeaman, MR
血小板杀微生物蛋白（PMP）是一种小分子阳离子肽，对常见的血流病原体（如金黄色葡萄球菌）具有有效的杀微生物活性。我们以前表明，S。在体外对凝血酶诱导的PMP（tPMP-1）表现出抗性的金黄色葡萄球菌菌株具有增强的引起人类和实验性心内膜炎的能力（T. Wu，M. R、Yeaman和A。S.帕耶，抗菌剂，化学药剂。38：729-732，1994; A. S，Payer等人，Antimicrob. Agents Chemother，42：3169-3172，1998; V.K. Dhawan ct al，，Infect. Immun，65：3293-3299，1997）。金黄色葡萄球菌没有被完全描绘。色葡萄金黄色葡萄球菌细胞膜似乎是tPMP-1作用的主要靶点。为了深入了解tPMP-1耐药的基础，我们比较了三种tPMP-1耐药细胞中膜结构和功能的几个参数，（tPMP-1（r））菌株及其遗传相关的tPMP-1敏感菌株tPMP-1（r）菌株通过三种不同的方法获得：转座子诱变、在体外存在tPMP-1的情况下连续传代、或携带天然存在的多抗性质粒（pSK 1）。发现所有tPMP-1（r）菌株都具有升高水平的长链、不饱和膜脂质，与它们的tPMP-1（s）对应物相比，这反映在菌株对中细胞膜流动性的相应差异上，其中tPMP-1（r）菌株表现出显著更高程度的流动性，如通过荧光偏振评估的。金黄色葡萄球菌菌株与体外tPMP-1抗性相关。
Platelet microbicidal proteins (PMPs) are small cationic peptides which possess potent microbicidal activities against common bloodstream pathogens, such as Staphylococcus aureus. We previously showed that S. aureus strains exhibiting resistance to thrombin-induced PMP (tPMP-1) in vitro have an enhanced capacity to cause human and experimental endocarditis (T. Wu, M. R, Yeaman, and A. S. Payer, Antimicrob, Agents Chemother. 38:729-732, 1994; A. S, Payer et al,, Antimicrob. Agents Chemother, 42:3169-3172, 1998; V. K.. Dhawan ct al,, Infect. Immun, 65:3293-3299, 1997), However, the mechanisms mediating tPMP-1 resistance in S. aureus are not fully delineated. The S. aureus cell membrane appears to be a principal target for the action of tPMP-1. To gain insight into the basis of tPMP-1 resistance, we compared several parameters of membrane structure and function in three tPMP-1-resistant (tPMP-1(r)) strains and their genetically related, tPMP-1-susceptible (tPMP-1(s)) counterpart strains, The tPMP-1(r) strains were derived by three distinct methods: transposon mutagenesis, serial passage in the presence of tPMP-1 in vitro, or carriage of a naturally occurring multiresistance plasmid (pSK1), All tPMP-1(r) strains were found to possess elevated levels of longer-chain, unsaturated membrane Lipids, in comparison to their tPMP-1(s) counterparts, This was reflected in corresponding differences in cell membrane fluidity in the strain pairs, with tPMP-1(r) strains exhibiting significantly higher degrees of fluidity as assessed by fluorescence polarization, These data provide further support for the concept that specific alterations in the cytoplasmic membrane of S. aureus strains are associated with tPMP-1 resistance in vitro.