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关于黏菌素的分子视角:作用模式、耐药遗传学及表型敏感性

A Molecular Perspective on Colistin and : Mode of Action, Resistance Genetics, and Phenotypic Susceptibility.

作者信息

Elias Rita, Duarte Aida, Perdigão João

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisboa, Portugal.

Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisboa, Portugal.

出版信息

Diagnostics (Basel). 2021 Jun 25;11(7):1165. doi: 10.3390/diagnostics11071165.

Abstract

is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for .

摘要

是一种杆状、有包膜的革兰氏阴性菌,与多种医院感染有关。多重耐药(MDR)菌株不断增加,治疗选择日益有限。黏菌素是一种长期使用的聚阳离子七肽,由于其对革兰氏阴性菌(包括MDR菌株)的活性而重新受到关注。然而,这种抗生素具有复杂的作用模式,仍在研究中,并且有许多副作用。黏菌素耐药性的获得主要与通过添加由多基因调控网络的基因产物合成的阳离子基团改变脂多糖A的净电荷有关。除了这些染色体基因的突变外,黏菌素耐药性也可通过获得质粒编码基因来实现。然而,黏菌素耐药性分子标记的多样性以及黏菌素的一些不良特性损害了黏菌素耐药性监测方法的可靠性。本综述重点关注黏菌素的作用和分子耐药机制,以及对其药物敏感性测试的具体限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ad8/8305994/39f570f31ca5/diagnostics-11-01165-g001.jpg

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