Liao Weichao, Quan Jingjing, Huang Lei, Zhou Mengyu, Zhang Chen, Chen Lina, Hu Huangdu, Zhou Junxin, Li Xi, Jiang Yan, Yu Yunsong, Zhao Dongdong, Zhou Jiancang
Department of Intensive Care Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Int J Antimicrob Agents. 2025 Jul;66(1):107495. doi: 10.1016/j.ijantimicag.2025.107495. Epub 2025 Mar 24.
Escherichia coli is a major pathogen, and the emergence of carbapenem-resistant E. coli (CREC) significantly restricts clinical treatment options. Polymyxins are considered the last-line treatment for CREC infections; however, the occurrence of polymyxin-resistant CREC, particularly following reports of plasmid-mediated colistin resistance (mcr), poses an increasing challenge.
In this study, we identified a polymyxin-resistant CREC strain isolated from the rectal swab of a patient hospitalized in a hematology ward. Antimicrobial susceptibility testings, S1-PFGE, Southern blot analysis, Conjugation Experiment, whole genome sequencing (WGS) and bioinformatic analysis were used to characterize the strain.
The strain showed resistance to all tested antimicrobial agents except tigecycline. By bioinformatic analysis, the strain was found to carry one copy of the mcr-1.1 gene and two copies of bla genes. One bla and the mcr-1.1 gene were co-located on a plasmid (pCDE2901_MCR-NDM), while the second bla gene resided on another plasmid (pCDE2901_NDM). The bla gene in pCDE2901_MCR-NDM was likely mobilized from pCDE2901_NDM via a transposon. The plasmid pCDE2901_NDM could successfully transferred from the donor strain CDE2901 to the recipient strain EC600, while the plasmid pCDE2901_MCR-NDM was unable to undergo horizontal transfer despite harboring mobile-associated genes.
Given the critical role of polymyxins in treating CREC infections, the co-transfer of polymyxin and carbapenem resistance may severely undermine the efficacy of clinical therapies. Strengthened surveillance and monitoring are imperative to curtail the spread of extensively drug-resistant (XDR) pathogens.
大肠杆菌是一种主要病原体，耐碳青霉烯类大肠杆菌（CREC）的出现显著限制了临床治疗选择。多粘菌素被认为是治疗CREC感染的最后一线药物；然而，耐多粘菌素CREC的出现，尤其是在质粒介导的粘菌素耐药性（mcr）报道之后，带来了越来越大的挑战。
在本研究中，我们从一名血液科住院患者的直肠拭子中鉴定出一株耐多粘菌素的CREC菌株。采用药敏试验、S1-PFGE、Southern印迹分析、接合实验、全基因组测序（WGS）和生物信息学分析对该菌株进行表征。
该菌株对除替加环素外的所有测试抗菌药物均耐药。通过生物信息学分析，发现该菌株携带一个mcr-1.1基因拷贝和两个bla基因拷贝。一个bla基因和mcr-1.1基因共位于一个质粒（pCDE2901_MCR-NDM）上，而第二个bla基因位于另一个质粒（pCDE2901_NDM）上。pCDE2901_MCR-NDM中的bla基因可能通过转座子从pCDE2901_NDM转移而来。质粒pCDE2901_NDM可以成功地从供体菌株CDE2901转移到受体菌株EC600，而质粒pCDE2901_MCR-NDM尽管含有与移动相关的基因，但无法进行水平转移。
鉴于多粘菌素在治疗CREC感染中的关键作用，多粘菌素耐药性和碳青霉烯类耐药性的共同转移可能严重削弱临床治疗的疗效。加强监测对于遏制广泛耐药（XDR）病原体的传播至关重要。
