Genetic organization of the chromosome region surrounding mecA in clinical staphylococcal strains:: Role of IS431-mediated mecI deletion in expression of resistance in mecA-carrying, low-level methicillin-resistant Staphylococcus haemolyticus

Genetic organization of the chromosome region surrounding mecA in clinical staphylococcal strains:: Role of IS431-mediated mecI deletion in expression of resistance in mecA-carrying, low-level methicillin-resistant Staphylococcus haemolyticus
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DOI:
10.1128/aac.45.7.1955-1963.2001
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发表时间:
2001-07-01
影响因子:
4.9
通讯作者:
Hiramatsu, K
Hiramatsu, K
中科院分区:
医学2区
文献类型:
--
作者:
Katayama, Y;Ito, T;Hiramatsu, K

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我们报道了38株耐甲氧西林金黄色葡萄球菌和91株耐甲氧西林凝固酶阴性葡萄球菌携带的mecA基因复合体的结构多样性,特别是它与甲氧西林耐药表型表达的相关性。最普遍和分布最广泛的mec复合体具有mecI-mecR1-mecA-IS431R(或IS431mec)结构,命名为A类mecA基因复合体。相反,在溶血性链球菌中,mecA被两个拷贝的IS431包围,形成IS431L-mecA-IS431R结构。38株溶血性S菌株中,有5株对甲氧西林低水平耐药(MIC1~4 mg/L),群体分析显示具有异质性耐甲氧西林的特点。在这5株菌株中,IS431L位于完整的mecI基因左侧,形成了IS431L-A类mecA-基因复合体结构。在其他溶血链球菌中,IS431L与mecI和mecR1的缺失有关,形成IS431L-Delta mecR1-mecA-IS431mec结构,命名为C类mecA基因复合体。突变株对具有中等水平的甲氧西林抗性(MIC值为16 mg/L),代表突变株SH621-37的mecA基因转录被下调。我们的研究表明,mecI编码的阻遏子功能是导致部分S临床分离株对甲氧西林低水平耐药的原因,IS431介导的mecI基因缺失通过mecA基因转录的去抑制导致甲氧西林耐药的表达。
We report on the structural diversity of mecA gene complexes carried by 38 methicillin-resistant Staphylococcus aureus and 91 methicillin-resistant coagulase-negative Staphylococcus strains of seven different species with a special reference to its correlation with phenotypic expression of methicillin resistance. The most prevalent and widely disseminated mec complex had the structure mecI-mecR1-mecA-IS431R (or IS431mec), designated the class A mecA gene complex. In contrast, in S. haemolyticus, mecA was bracketed by two copies of IS431, forming the structure IS431L-mecA-IS431R. Of the 38 S, haemolyticus strains, 5 had low-level methicillin resistance (MIC, 1 to 4 mg/liter) and characteristic heterogeneous methicillin resistance as judged by population analysis. In these five strains, IS431L was located to the left of an intact mecI gene, forming the structure IS431L-class A mecA-gene complex. In other S. haemolyticus strains, IS431L was associated with the deletion of mecI and mecR1, forming the structure IS431L-Delta mecR1-mecA-IS431mec, designated the class C mecA gene complex, Mutants with the class C mecA gene complex were obtained in vitro by selecting strain SH621, containing the IS431L-class A mecA gene complex with low concentrations of methicillin (1 and 3 mg/liter). The mutants had intermediate level of methicillin resistance (MIC, 16 to 64 mg/liter), The mecA gene transcription was shown to be derepressed in a representative mutant strain, SH621-37. Our study indicated that the mecI-encoded repressor function is responsible for the low-level methicillin resistance of some S, haemolyticus clinical strains and that the IS431-mediated mecI gene deletion causes the expression of methicillin resistance through the derepression of mecA gene transcription.