首页> 美国卫生研究院文献>Antimicrobial Agents and Chemotherapy >Cell Wall Thickening Is Not a Universal Accompaniment of the Daptomycin Nonsusceptibility Phenotype in Staphylococcus aureus: Evidence for Multiple Resistance Mechanisms
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Cell Wall Thickening Is Not a Universal Accompaniment of the Daptomycin Nonsusceptibility Phenotype in Staphylococcus aureus: Evidence for Multiple Resistance Mechanisms

机译:细胞壁增厚不是金黄色葡萄球菌达托霉素不易感表型的普遍伴奏:多重耐药机制的证据。

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摘要

The mechanism(s) of daptomycin (DAP) resistance (DAPr) is incompletely defined. Thickened cell walls (CWs) acting as either a mechanical barrier or an affinity trap for DAP have been purported to be a major contributor to the DAPr phenotype. To this end, we studied an isogenic set of methicillin-resistant Staphylococcus aureus (MRSA) isolates (pulsotype USA 300) from the bloodstream of a DAP-treated patient with endocarditis in which serial strains exhibited increasing DAPr. Of interest, the DAPr isolate differed from its parental strain in several parameters, including acquisition of a point mutation within the putative synthase domain of the mprF gene in association with enhanced mprF expression, increased synthesis of lysyl-phosphotidylglycerol, an enhanced positive envelope charge, and reduced DAP surface binding. Transmission electron microscopy (TEM) revealed no significant increases in CW thickness in the two DAPr isolates (MRSA 11/21 and REF2145) compared with that in the DAP-susceptible (DAPs) parental strain, MRSA 11/11. The rates of Triton X-100-induced autolysis were also identical for the strain set. Furthermore, among six additional clinically isolated DAPs/DAPr S. aureus strain pairs, only three DAPr isolates exhibited CWs significantly thicker than those of the respective DAPs parent. These data confirm that CW thickening is neither universal to DAPr S. aureus nor sufficient to yield the DAPr phenotype among S. aureus strains.
机译:达托霉素(DAP)耐药性(DAP r )的机制尚未完全确定。据称,用作DAP的机械屏障或亲和阱的细胞壁增厚(CW)是DAP r 表型的主要贡献者。为此,我们研究了来自DAP治疗的心内膜炎患者血流中的耐甲氧西林金黄色葡萄球菌(MRSA)分离株(脉冲型USA 300)的等基因组,其中系列菌株显示DAP r 。有趣的是,DAP r 分离株在几个参数上不同于其亲本菌株,包括在mprF基因的假定合酶结构域内获得点突变以及增强的mprF表达,增加了赖氨酰磷脂酰甘油,增强的正包膜电荷和降低的DAP表面结合。透射电子显微镜(TEM)显示,与DAP敏感性(DAP s)相比,两种DAP r 菌株(MRSA 11/21和REF2145)的CW厚度均没有显着增加。 sup>)亲本菌株,MRSA 11/11。 Triton X-100诱导的自溶速率对于菌株组也相同。此外,在另外六个临床分离的DAP s / DAP r 金黄色葡萄球菌菌株对中,只有三个DAP r 分离株表现出比那些更厚的CW。 DAP s 父对象的名称。这些数据证实CW增稠既不是DAP r 金黄色葡萄球菌的普遍特征,也不足以产生金黄色葡萄球菌菌株中的DAP r 表型。

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