Role of insertion elements and yycFG in the development of decreased susceptibility to vancomycin in Staphylococcus aureus
Role of insertion elements and yycFG in the development of decreased susceptibility to vancomycin in Staphylococcus aureus
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DOI：
10.1016/j.ijmm.2007.02.002
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发表时间：
2007-07-01
影响因子：
4.1
通讯作者：
Bierbaum, Gabriele
中科院分区：
文献类型：
--
作者：
Jansen, Andrea;Tuerck, Michael;Bierbaum, Gabriele
糖肽抗生素万古霉素通过与细胞质膜中细胞壁前体脂质11的D-丙氨酰-D-丙氨酸末端结合而发挥作用。本研究的目的是鉴定可能参与万古霉素耐药机制的基因。为此，使用金黄色葡萄球菌全基因组芯片分析了两种万古霉素中度耐药金黄色葡萄球菌（VISA）菌株、临床分离金黄色葡萄球菌SA I 37/93A（Etest：8μg/ml）及其实验室突变体金黄色葡萄球菌SA I 37/93G（Etest：12μg/ml）的表达谱。结果表明，重要的双组分调节系统 yycF (vicR) 和 yycG (vicK) 在菌株 SA137/93A 中急剧上调。对菌株 SA137/93A 的 yycFG 启动子区域进行测序表明，在预测的启动子区域中插入了 IS256，从而产生了潜在更强的杂合启动子。在菌株 SA137/93G 中，IS256 未整合到 yycFG 启动子区域中，但在之前的研究中，已发现 IS256 的副本使 tcaA 基因失活（Maki 等人 Antimicrob. Agents and Chemother. 48, 1953-1959 (2004)）。详细的群体分析表明，除了 SCCmec 的丧失之外，tcaA 的失活似乎至少部分导致菌株 SA137/93G 中替考拉宁和万古霉素耐药性的增加。 (C) 2007 爱思唯尔有限公司。版权所有。
The glycopeptide antibiotic vancomycin acts by binding to the D-alanyl-D-alanine terminus of the cell wall precursor lipid 11 in the cytoplasmic membrane. The purpose of this study was the identification of genes that might be involved in the vancomycin resistance mechanism. To this end, the expression profiles of two vancomycin intermediately resistant Staphylococcus aureus (VISA) strains, the clinical isolate S. aureus SA I 37/93A (Etest: 8 mu g/ml) and its laboratory mutant S. aureus SA I 37/93G (Etest: 12 mu g/ml) were analyzed using an S. aureus full-genome chip. The results indicated that an essential two-component regulatory system, yycF (vicR) and yycG (vicK) was drastically up-regulated in strain SA137/93A. Sequencing of the yycFG promoter region of strain SA137/93A revealed an insertion of IS256 in the predicted promoter region creating a potentially stronger hybrid promoter. In strain SA137/ 93G, IS256 was not integrated in the yycFG promoter region but, in previous studies, a copy of IS256 had been found to inactivate the tcaA gene (Maki et al. Antimicrob. Agents and Chemother. 48, 1953-1959 (2004)). Detailed population analyses showed that, in addition to the loss of SCCmec, the inactivation of tcaA seems to cause at least part of the increase in teilcoplanin and vancomycin resistance in strain SA137/93G. (C) 2007 Elsevier GmbH. All rights reserved.