Genetic changes associated with glycopeptide resistance in Staphylococcus aureus: predominance of amino acid substitutions in YvqF/VraSR
Genetic changes associated with glycopeptide resistance in Staphylococcus aureus: predominance of amino acid substitutions in YvqF/VraSR
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DOI：
10.1093/jac/dkp394
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发表时间：
2010-01-01
影响因子：
5.2
通讯作者：
Maebashi, Kazunori
中科院分区：
文献类型：
--
作者：
Kato, Yoshihisa;Suzuki, Takahisa;Maebashi, Kazunori
为了进一步了解实验室来源和临床分离的金黄色葡萄球菌中由多种内源性突变引起的中等水平糖肽耐药的机制。在使用多种细胞壁活性抗生素的选择下产生金黄色葡萄球菌菌株。27个基因的完整序列，包括17个双组分组氨酸激酶传感器，然后与它们的敏感亲本菌株进行比较。对125例临床分离的沙门氏菌进行了遗传学分析。金黄色葡萄球菌分离株和42个地理上不同的万古霉素中间体S.使用亚胺培南的选择性压力导致单点突变，导致两个基因中的氨基酸取代：vraS，编码双组分组氨酸激酶传感器;和SA 1702（也称为yvqF，位于vraS的紧上游），编码保守的假设蛋白。两种不同蛋白质MsrR（一种肽蛋氨酸亚砜还原酶调节剂）和TcaA（一种替考拉宁耐药相关蛋白）中突变的累积与糖肽MIC的进一步增加相关。125株临床分离株中YvqF/VraSR突变体的患病率沿着相应替考拉宁MIC如下：0%（0/39），< 1 mg/L; 48.6%（17/35），2 mg/L; 72.7%（24/33），4 mg/L; 93.8%（15/16），8 mg/L;和100%（2/2），16 mg/L。对42株VISA分离株的基因分析也发现了YvqF/VraS的主要氨基酸替换，9株（21.4%）发现YvqF突变，7株（16.7%）发现VraS突变。替考拉宁敏感性降低的金黄色葡萄球菌分离株。
To further understand the mechanism of intermediate-level glycopeptide resistance, resulting from multiple endogenous mutations, in both laboratory-derived and clinically isolated Staphylococcus aureus.Laboratory-derived S. aureus strains were generated under selection using a variety of cell-wall-active antibiotics. Complete sequences of 27 genes, including 17 two-component histidine kinase sensors, were then compared with those of their susceptible parent strain. Further genetic analysis was performed on 125 clinical S. aureus isolates and 42 geographically diverse isolates of vancomycin-intermediate S. aureus (VISA).Selective pressure using imipenem resulted in single point mutations leading to amino acid substitutions in two genes: vraS, encoding a two-component histidine kinase sensor; and SA1702 (also called yvqF, located immediately upstream of vraS), encoding a conserved hypothetical protein. The accumulation of the mutation in two distinct proteins-MsrR, a peptide methionine sulphoxide reductase regulator, and TcaA, a teicoplanin-resistance-associated protein-correlated with further increases in the glycopeptide MIC. The prevalence of YvqF/VraSR mutants among 125 clinical isolates along with the corresponding teicoplanin MICs was as follows: 0% (0/39), < 1 mg/L; 48.6% (17/35), 2 mg/L; 72.7% (24/33), 4 mg/L; 93.8% (15/16), 8 mg/L; and 100% (2/2), 16 mg/L. Genetic analysis of 42 VISA isolates also identified the predominant amino acid substitutions in YvqF/VraS: 9 isolates (21.4%) revealed mutations in YvqF, followed by 7 isolates with mutations in VraS (16.7%).Our findings provide novel insights into the high prevalence and genetic diversity of YvqF/VraSR mutants among clinical S. aureus isolates with reduced susceptibility to teicoplanin.