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鲍曼不动杆菌 PmrAB 基因座过表达与氨基酸取代与多黏菌素耐药的相关性。

Correlation between overexpression and amino acid substitution of the PmrAB locus and colistin resistance in Acinetobacter baumannii.

机构信息

Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.

出版信息

Int J Antimicrob Agents. 2011 Jun;37(6):525-30. doi: 10.1016/j.ijantimicag.2011.02.008. Epub 2011 Apr 14.

DOI:10.1016/j.ijantimicag.2011.02.008
PMID:21497062
Abstract

Relationships between the PmrAB two-component system and colistin resistance were investigated in Acinetobacter baumannii. The sequences of pmrA, pmrB and pmrC in 26 colistin-susceptible (ColS) and 7 colistin-resistant (ColR) A. baumannii isolates were determined. In addition, 30 ColR mutants (colistin minimum inhibitory concentration >64 mg/L) were selected in vitro from 10 ColS strains and the pmrA, pmrB and pmrC sequences of the in-vitro-selected ColR mutants were also determined. Expression of pmrA and pmrB was compared between the ColR mutants and their parent ColS strains using a quantitative real-time polymerase chain reaction method. Elevated expression of pmrA and pmrB genes was evident both in wild-type and in in-vitro-selected ColR strains. However, no amino acid differences in the pmrA, pmrB and pmrC genes were found between wild-type ColR and ColS isolates. Although six kinds of amino acid alterations in pmrB were identified in in-vitro-selected ColR mutants, no changes were found in some of the mutants. These findings indicate that increased expression of the PmrAB system is essential for colistin resistance in A. baumannii but that amino acid alterations might be only partially responsible for resistance.

摘要

研究了鲍曼不动杆菌中 PmrAB 两组分系统与多粘菌素耐药性的关系。测定了 26 株多粘菌素敏感(ColS)和 7 株多粘菌素耐药(ColR)鲍曼不动杆菌分离株的 pmrA、pmrB 和 pmrC 序列。此外,从 10 株 ColS 株中体外选择了 30 株 ColR 突变株(最低抑菌浓度多粘菌素>64mg/L),并测定了体外选择的 ColR 突变株的 pmrA、pmrB 和 pmrC 序列。通过实时定量聚合酶链反应方法比较了 ColR 突变株与其亲本 ColS 株之间 pmrA 和 pmrB 的表达。野生型和体外选择的 ColR 株中 pmrA 和 pmrB 基因的高表达均明显。然而,在野生型 ColR 和 ColS 分离株之间未发现 pmrA、pmrB 和 pmrC 基因中的氨基酸差异。尽管在体外选择的 ColR 突变体中鉴定出 pmrB 中的六种氨基酸改变,但在一些突变体中未发现变化。这些发现表明,PmrAB 系统的过度表达是鲍曼不动杆菌对多粘菌素耐药性的必要条件,但氨基酸改变可能只是部分负责耐药性。

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