Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens
Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens
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DOI：
10.1128/aac.00580-17
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发表时间：
2017-06-01
影响因子：
4.9
通讯作者：
Doi, Yohei
中科院分区：
文献类型：
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作者：
Liu, Yi-Yun;Chandler, Courtney E.;Doi, Yohei
mcr-1最初被报道为中国大肠杆菌和肺炎克雷伯菌临床分离株中第一个质粒介导的粘菌素耐药基因，随后在世界范围内肠杆菌科的各种物种中被发现。mcr-1编码磷酸乙醇胺转移酶，其表达已被证明在大肠杆菌中产生磷酸乙醇胺修饰的双磷酸化六酰化脂质a。在这里，我们研究了mcr-1对实验室和临床革兰氏阴性ESKAPE（粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌）病原菌的粘菌素敏感性和脂多糖结构的影响，这些病原菌在临床上经常使用粘菌素治疗。采用MIC法测定大肠杆菌、肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌实验室和临床菌株的mcr-1对粘菌素耐药性的影响。质谱分析MCR-1引起的脂质A结构变化。mcr-1的引入导致大肠杆菌、肺炎克雷伯菌和鲍曼假杆菌对粘菌素产生耐药性，但铜绿假单胞菌对粘菌素的敏感性仅略有降低。磷酸乙醇胺对脂质A的修饰在所有四种物种中都是一致的。这些发现强调了ESKAPE病原菌中mcr-1的表达导致粘菌素耐药的风险，特别是在肺炎克雷伯菌和鲍曼芽胞杆菌中。此外，观察到脂质A结构被改变，尽管在某些情况下黏菌素mic只有适度增加，这表明可能需要开发更复杂的监测方法来跟踪mcr-1或质粒介导的磷酸乙醇胺转移酶的传播。
mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmid-mediated phosphoethanolamine transferases in general.