Impact of mecA promoter mutations on mecA expression and β-lactam resistance levels
Impact of mecA promoter mutations on mecA expression and β-lactam resistance levels
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DOI：
10.1016/j.ijmm.2008.01.015
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发表时间：
2008-10-01
影响因子：
4.1
通讯作者：
Berger-Baechi, Brigitte
中科院分区：
文献类型：
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作者：
Ender, Miriam;McCallum, Nadine;Berger-Baechi, Brigitte
在瑞士苏黎世的注射吸毒者中流行的所谓“药物克隆”（耐甲氧西林金黄色葡萄球菌）中，苯唑西林耐药性水平极低的原因可追溯到mecA启动子序列，特别是菌株的遗传背景。对其nice复合物的测序鉴定了一个点突变（TATACT到TATATT），在mecA启动子/操纵基因区的-10区域产生了一个完美的回文序列，该区域含有mecA阻遏蛋白MecI和BlaI的结合位点。两种具有非常不同的β-内酰胺抗性表型的菌株，低水平抗性药物克隆型菌株CHE 482和高度均一抗性菌株COLn，被去除它们的SCCmec元件，随后用含有在野生型或突变型启动子控制下的mecA的质粒转化。表达研究表明，该突变对mecA转录和相应的PBP 2a产生都有显著影响，但在给定的遗传背景下对β-内酰胺抗性水平的影响很小。mecA核糖体结合位点的进一步突变（GGAGG至GGAGT）。与SCCmec IV型菌株相同，发现对β-内酰胺酶转录和PBP 2a含量没有可辨别的影响，并且对β-内酰胺抗性只有最小的影响。与引入这些不同控制的mecA基因的遗传背景相关的因素对β-内酰胺抗性水平的影响比mecA转录速率的影响大得多。这种药物克隆对mecA表达的严格抑制以及β-内酰胺的缺乏可能有助于这种快速生长菌株的明显适应性。(C)2008年Elsevier GmbH。All rights reserved.
The reason for the extremely low-level oxacillin resistance in a so-called 'drug clone', a methicillin-resistant Staphylococcus aureus circulating among injection drug users in Zurich, Switzerland, could be traced back to the mecA Promoter sequence and particularly to the strain's genetic background. Sequencing of its nice complex identified a point Mutation (TATACT to TATATT), creating a perfect palindrome in the -10 region of the mecA promoter/operator region containing the binding sites For the mecA repressors MecI and BlaI. Two strains with vastly different beta-lactam resistance phenotypes, the low-level resistant drug Clone type strain CHE482 and the highly homogeneously resistant strain COLn, were cured of their SCCmec elements and subsequently transformed with plasmids containing mecA under the control of either the wild-type or mutant promoter. Expression Studies showed that this mutation had significant effects on both mecA transcription and corresponding PBP2a production, but only small effects on beta-lactam resistance levels within a given genetic background. A Further mutation in the mecA ribosomal binding site (GGAGG to GGAGT). common to SCCmec type IV strains, was found to have no discernable effect oil me(A transcription and PBP2a content, and only minimal effects on beta-lactam resistance. Factors associated with the genetic backgrounds into which these differently controlled mecA genes were introduced had a Much higher impact on P-lactam resistance levels than the rates of mecA transcription. The tight repression of mecA expression this drug clone the absence of beta-lactams Could contribute to the apparent fitness of this Fast growing strain. (C) 2008 Elsevier GmbH. All rights reserved.