背景:耐碳青霉烯的大肠杆菌(CREco)由于其多重耐药性而构成了重大的公共卫生威胁。粘菌素通常是针对CREco的最后手段;但是,粘菌素抗性基因mcr-1的出现使治疗方案复杂化。
方法:两种大肠杆菌菌株(ECO20和ECO21),从不同病房的住院患者中恢复,表现出对碳青霉烯类和粘菌素的抗性。全基因组测序和表型表征用于研究抗性模式,质粒谱,抗性和毒力基因的可转移性,和铁载体生产能力。比较基因组分析用于研究mcr-1,blaNDM-7和毒力簇的遗传环境。
结果:两种大肠杆菌菌株均表现出mcr-1和blaNDM-7基因的存在,对多种抗生素表现出高耐药性。基因组分析揭示了这些菌株的克隆传播,具有相同的质粒谱(pMCR,pNDM,和pVir)与粘菌素抗性有关,耐碳青霉烯,和毒力因子。共轭实验证实了这些质粒的可转移性,表明它们有可能向其他菌株传播抗性和毒力特性。比较基因组分析揭示了mcr-1(IncX4型)和blaNDM(IncX3型)质粒在不同细菌物种中的分布,强调他们的适应性和威胁。pVir的新颖性表明其在驱动高度适应性和致病性菌株进化中的潜在作用。
结论:我们的发现强调了mcr-1,blaNDM-7和产生铁载体的质粒在大肠杆菌中的共同出现,这对全球健康构成了重大关切。这项研究对于解开控制质粒转移和重组的复杂机制以及设计强大的策略来控制其在医疗保健环境中的传播至关重要。
BACKGROUND: Carbapenem-resistant E. coli (CREco) pose a significant public health threat due to their multidrug resistance. Colistin is often a last-resort treatment against CREco; however, the emergence of colistin resistance gene mcr-1 complicates treatment options.
METHODS: Two E. coli strains (ECO20 and ECO21), recovered from hospitalized patients in distinct wards, exhibited resistance to carbapenems and colistin. Whole-genome sequencing and phenotypic characterization were employed to study resistance patterns, plasmid profiles, transferability of resistance and virulence genes, and siderophore production capabilities. Comparative genome analysis was used to investigate the genetic environment of mcr-1, blaNDM-7, and virulence clusters.
RESULTS: Both E. coli strains exhibited thr presence of both mcr-1 and blaNDM-7 genes, showing high resistance to multiple antibiotics. Genomic analysis revealed the clonal transmission of these strains, possessing identical plasmid profiles (pMCR, pNDM, and pVir) associated with colistin resistance, carbapenem resistance, and virulence factors. Conjugation experiments confirmed the transferability of these plasmids, indicating their potential to disseminate resistance and virulence traits to other strains. Comparative genomic analyses unveiled the distribution of mcr-1 (IncX4-type) and blaNDM (IncX3-type) plasmids across diverse bacterial species, emphasizing their adaptability and threat. The novelty of pVir indicates its potential role in driving the evolution of highly adaptable and pathogenic strains.
CONCLUSIONS: Our findings underscore the co-occurrence of mcr-1, blaNDM-7, and siderophore-producing plasmids in E. coli, which poses a significant concern for global health. This research is crucial to unravel the complex mechanisms governing plasmid transfer and recombination and to devise robust strategies to control their spread in healthcare settings.