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MgrB 失活导致海氏肠杆菌亚种对黏菌素获得性耐药。

MgrB Inactivation Is Responsible for Acquired Resistance to Colistin in Enterobacter hormaechei subsp. .

机构信息

Laboratoire de Microbiologie Fondamentale et Pathogénicité (MFP), Université de Bordeaux, CNRS UMR-5234, Bordeaux, France.

Laboratoire des Biopesticides, Centre de Biotechnologie de Sfax, Sfax, Tunisia.

出版信息

Antimicrob Agents Chemother. 2020 May 21;64(6). doi: 10.1128/AAC.00128-20.

DOI:10.1128/AAC.00128-20
PMID:32253218
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7269514/
Abstract

Multidrug-resistant strains belonging to the complex (ECC) group, and especially those belonging to clusters C-III, C-IV, and C-VIII, have increasingly emerged as a leading cause of health care-associated infections, with colistin used as one of the last lines of treatment. However, colistin-resistant ECC strains have emerged. The aim of this study was to prove that MgrB, the negative regulator of the PhoP/PhoQ two-component regulatory system, is involved in colistin resistance in ECC of cluster C-VIII, formerly referred to as subsp. An mutant (Eh22-Mut) was selected from a clinical isolate of Eh22. The sequencing analysis of its gene showed the presence of one nucleotide deletion leading to the formation of a truncated protein of six instead of 47 amino acids. The wild-type gene from Eh22 and that of a clinical strain of used as controls were cloned, and the corresponding recombinant plasmids were used for complementation assays. The results showed a fully restored susceptibility to colistin and confirmed for the first time that gene expression plays a key role in acquired resistance to colistin in ECC strains.

摘要

属于 复合体(ECC)群的多药耐药菌株,尤其是属于 C-III、C-IV 和 C-VIII 簇的那些菌株,已成为导致医疗保健相关性感染的主要原因之一,而黏菌素被用作最后治疗手段之一。然而,已经出现了对黏菌素耐药的 ECC 菌株。本研究旨在证明MgrB,即 PhoP/PhoQ 双组分调控系统的负调控因子,参与了以前称为 亚种的 C-VIII 簇 ECC 中的黏菌素耐药性。从临床分离株 Eh22 中选择了一个 突变体(Eh22-Mut)。对其 基因的测序分析表明,存在一个核苷酸缺失,导致形成一个截断蛋白,只有六个氨基酸而不是 47 个氨基酸。从 Eh22 和用作对照的 临床株中克隆了野生型 基因,并使用相应的重组质粒进行了互补测定。结果表明,对黏菌素的敏感性完全恢复,并首次证实 基因表达在 ECC 菌株获得性对黏菌素耐药性中起着关键作用。

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