Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.
Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.
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DOI：
10.3346/jkms.2006.21.5.827
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发表时间：
2006-10
影响因子：
4.5
通讯作者：
Kim MJ
中科院分区：
文献类型：
--
作者：
Yang JA;Park DW;Sohn JW;Yang IS;Kim KH;Kim MJ
近年来，越来越多地报道了葡萄球菌中低水平莫匹罗星耐药性的出现和传播。本研究的目的是鉴定具有低水平莫匹罗星耐药性的耐甲氧西林金黄色葡萄球菌 (MRSA) 临床分离株中染色体异亮氨酰-tRNA 合成酶基因 (ileS) 内的错义突变。从重症监护病房的 79 名患者中收集了 6 个月的 20 株具有低水平莫匹罗星耐药性（最低抑菌浓度 16-64 µg/mL）的 MRSA 菌株。对分离株进行了异亮氨酰-tRNA 合成酶 (IleS) 突变分析，该突变可能影响莫匹罗星与金黄色葡萄球菌 IleS 酶三维结构的结合。所有具有低水平莫匹罗星耐药性的分离株均含有影响罗斯曼折叠的已知 V588F 突变，其中一些还具有先前未识别的突变，如 P187F、K226T、F227L、Q612H 或 V767D。有趣的是，Q612H 是一种新的突变，涉及稳定含有 KMSKS 基序的催化环的构象。总之，本研究证实ileS基因的分子异质性在低水平莫匹罗星耐药的临床MRSA分离株中很常见，需要对临床突变体进行进一步研究以了解低水平莫匹罗星耐药的结构基础。
Emergence and spread of low-level mupirocin resistance in staphylococci have been increasingly reported in recent years. The aim of this study was to characterize missense mutations within the chromosomal isoleucyl-tRNA synthetase gene (ileS) among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) with low-level mupirocin resistance. A total of 20 isolates of MRSA with low-level mupirocin resistance (minimal inhibitory concentration, 16-64 µg/mL) were collected from 79 patients in intensive care units for six months. The isolates were analyzed for isoleucyl-tRNA synthetase (IleS) mutations that might affect the binding of mupirocin to the three-dimensional structure of the S. aureus IleS enzyme. All isolates with low-level mupirocin resistance contained the known V588F mutation affecting the Rossman fold, and some of them additionally had previously unidentified mutations such as P187F, K226T, F227L, Q612H, or V767D. Interestingly, Q612H was a novel mutation that was involved in stabilizing the conformation of the catalytic loop containing the KMSKS motif. In conclusion, this study confirms that molecular heterogeneity in ileS gene is common among clinical MRSA isolates with low-level mupirocin resistance, and further study on clinical mutants is needed to understand the structural basis of low-level mupirocin resistance.
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影响因子：
9.4
作者：
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通讯作者：
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