MCR-1介导多黏菌素耐药性的分子机制研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-1058

摘要/Abstract

摘要：

多黏菌素耐药基因mcr-1的出现为临床感染治疗带来了新的挑战。自其发现以来，已有6大洲61个不同的国家或地区报道了mcr-1的流行。为了遏制mcr-1的流行，我国农业农村部颁布了禁用多黏菌素作为饲料添加剂的禁令。尽管已有研究指出停用多黏菌素作为动物饲料添加剂可有效降低动物源、环境源和人源样本中mcr-1阳性菌的检出率，但是mcr-1在临床上仍呈低流行性的状态。截至目前已经发现34种mcr-1突变体和9种不同的MCR家族蛋白，未来是否会进化出流行率更高的MCR亚型也有待观察。关于mcr-1介导多黏菌素耐药的分子机制及其影响细菌细胞壁的机制也有新的成果不断出现。本文将对mcr-1的流行性、耐药机制及其对细菌适应性影响的分子机制3个方面的最新进展进行简要综述，以期为遏制多黏菌素耐药基因mcr-1的传播提供可参考依据。

关键词: 抗生素, mcr-1, 多黏菌素, 耐药性, 质粒

Abstract:

The emergence of the polymyxin resistance gene mcr-1 has brought new challenges to the treatment of clinical infections. mcr-1 has been reported from 61 different countries or territories on 6 continents after its discovery. In order to curb the spreading of mcr-1, Chinese Ministry of Agriculture and Rural Affairs proposed a compulsory official banning of polymyxin as a feed additives. Although previous studies have shown that the withdrawal of polymyxin from an animal feed additive may effectively reduce the prevalence of mcr-1 positive bacteria in animal, environmental and human samples, the mcr-1 prevalence fluctuated at a low level. Up to now, 34 mcr-1 variants and 9 different MCR family proteins have been found. It remains to be seen whether they will evolve into a more prevalent MCR subtypes. In addition, recent studies have explored the molecular mechanism of mcr-1-mediated polymyxin resistance and its effect on the bacterial cell wall. This article briefly reviews the latest progress of mcr-1 on epidemic, drug resistance mechanism, and mechanism affecting bacterial fitness cost, aiming to provide a reference for curbing the spread of the polymyxin resistance gene mcr-1.

Key words: antibiotics, mcr-1, polymyxin, drug resistance, plasmids

陈勇, 李亚鑫, 王亚瑄, 梁露洁, 冯思源, 田国宝. MCR-1介导多黏菌素耐药性的分子机制研究进展[J]. 生物技术通报, 2023, 39(6): 102-108.

CHEN Yong, LI Ya-xin, WANG Ya-xuan, LIANG Lu-jie, FENG Si-yuan, Tian Guo-bao. Research Progress in the Molecular Mechanism of MCR-1 Mediated Polymyxin Resistance[J]. Biotechnology Bulletin, 2023, 39(6): 102-108.

图/表 1

图1 MCR-1介导细菌产生多黏菌素的耐药机制 MCR-1将磷脂酰乙醇胺（PE）分子上带正电荷的磷酸乙醇胺（PEA）基团转移到细菌细胞外膜上的磷脂A，生成PEA-4' Lipid A，使细菌细胞膜上的正电荷增多，从而降低多黏菌素与脂多糖的亲和力，最终导致低水平耐药表型的产生

Fig. 1 Resistance mechanism of MCR-1-mediated bacterium producing polymyxin MCR-1 transfers the positively charged phosphoethanolamine（PEA）group on the phosphatidylethanolamine（PE）molecule to the phospholipid A on the bacterial cell outer membrane to generate PEA-4' Lipid A, which increases the positive charge on the bacterial cell membrane, thus reducing the affinity of polymyxin and lipopolysaccharide, and ultimately leads to the generation of low-level drug resistance phenotype

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