Global epidemiology, genetic environment, risk factors and therapeutic prospects of mcr genes: A current and emerging update.
Global epidemiology, genetic environment, risk factors and therapeutic prospects of mcr genes: A current and emerging update.
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全球流行病学，遗传环境，危险因素和MCR基因的治疗前景：当前和新兴的更新。
DOI：
10.3389/fcimb.2022.941358
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
移动的粘菌素抗性（mcr）基因修饰脂多糖的脂质A分子，改变外膜的总体电荷。迄今为止，已在11种肠杆菌科菌种中描述了10种mcr基因，其中大肠埃希菌、肺炎克雷伯菌和沙门氏菌属是最主要的。它们在全球72个国家存在，由于在家禽中使用粘菌素促进生长和治疗肠道感染，目前动物标本的发病率最高。mcr从食用动物到肉类、粪便、环境和废水样本的广泛传播增加了通过食源性和病媒传播途径传播给人类的风险。mcr基因的稳定性和扩散由移动的遗传元件介导，如IncHI 2接合质粒，其与多个mcr基因和其他抗生素耐药基因相关。补偿性适应机制降低了获得mcr的成本。MCR蛋白在结构上和通过酶促作用是非常保守的。因此，发现对MCR-1有效的治疗剂应针对剩余的MCR蛋白进行测试。mcr基因在临床环境中的传播限制了可用的治疗方案，威胁着公共卫生。联合治疗是管理和治疗粘菌素耐药肠杆菌科感染同时降低粘菌素毒性作用的有希望的选择。
Mobile colistin resistance (mcr) genes modify Lipid A molecules of the lipopolysaccharide, changing the overall charge of the outer membrane. Ten mcr genes have been described to date within eleven Enterobacteriaceae species, with Escherichia coli, Klebsiella pneumoniae, and Salmonella species being the most predominant. They are present worldwide in 72 countries, with animal specimens currently having the highest incidence, due to the use of colistin in poultry for promoting growth and treating intestinal infections. The wide dissemination of mcr from food animals to meat, manure, the environment, and wastewater samples has increased the risk of transmission to humans via foodborne and vector-borne routes. The stability and spread of mcr genes were mediated by mobile genetic elements such as the IncHI2 conjugative plasmid, which is associated with multiple mcr genes and other antibiotic resistance genes. The cost of acquiring mcr is reduced by compensatory adaptation mechanisms. MCR proteins are well conserved structurally and via enzymatic action. Thus, therapeutics found effective against MCR-1 should be tested against the remaining MCR proteins. The dissemination of mcr genes into the clinical setting, is threatening public health by limiting therapeutics options available. Combination therapies are a promising option for managing and treating colistin-resistant Enterobacteriaceae infections whilst reducing the toxic effects of colistin.