Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University , Seoul, Republic of Korea.
Virulence. 2021 Dec;12(1):150-164. doi: 10.1080/21505594.2020.1867421.
Polymyxin B (PMB) is increasingly used as a last-line antibiotic; however, the emergence of PMB resistance is a serious threat to global health. Here, a total of 40 clinical isolates were collected to screen for PMB-resistant strains. Several clinical isolates including NCCP 16007 were far more resistant to PMB (MIC: 128-256 μg/ml) than the ATCC 17978 strain (MIC: 2 μg/ml) and appeared to possess resistance to broad-spectrum antibiotics including meropenem and 12 others. Four highly PMB-resistant strains possessed point mutations in the histidine kinase PmrB, leading to an increased expression of encoding a phosphoethanolamine transferase. Whole-genome analyses revealed that the NCCP 16007 stain had acquired two additional copies of the gene with phage integrase and 13 antibiotic resistance genes (ARGs) from other pathogens, including and . The GC ratios of the ARGs (50-60%) were higher than that of the chromosomal backbone (39.06%), further supporting the horizontal gene transfer of ARGs. Comparative genomics with other multidrug-resistant strains revealed that the NCCP 16007 strain has many additional ARGs and has lost several virulence factors including Csu pili and heme oxygenase but exhibited high pathogenicity in -infection models. The observation of condensed biofilm through confocal and scanning electron microscopy suggested that the NCCP 16007 strain may possess high adhesion capacity during urinary tract infection. Therefore, our genomic and phenotypic analyses suggested that the multidrug-resistant NCCP 16007 strain possesses high genome plasticity, natural transformation ability, and pathogenicity.
多粘菌素 B (PMB) 作为一种最后一线抗生素被越来越多地使用；然而，PMB 耐药性的出现对全球健康构成了严重威胁。在这里，共收集了 40 株临床分离株，以筛选 PMB 耐药株。一些临床分离株，包括 NCCP 16007，对 PMB 的耐药性远远高于 ATCC 17978 株（MIC：2μg/ml），且似乎对包括美罗培南在内的 12 种其他广谱抗生素具有耐药性。4 株高度 PMB 耐药株在组氨酸激酶 PmrB 中存在点突变，导致编码磷酸乙醇胺转移酶的表达增加。全基因组分析显示，NCCP 16007 株获得了两个额外的 基因拷贝，该基因带有噬菌体整合酶和来自其他病原体的 13 个抗生素耐药基因 (ARGs)，包括 和 。ARGs 的 GC 比值（50-60%）高于染色体骨架的 GC 比值（39.06%），进一步支持了 ARGs 的水平基因转移。与其他多药耐药 菌株的比较基因组学显示，NCCP 16007 菌株具有许多额外的 ARGs，并且失去了包括 Csu 菌毛和血红素氧化酶在内的几种毒力因子，但在 感染模型中表现出高致病性。通过共聚焦和扫描电子显微镜观察到浓缩生物膜的现象表明，NCCP 16007 菌株在尿路感染中可能具有高粘附能力。因此，我们的基因组和表型分析表明，多药耐药 NCCP 16007 菌株具有高基因组可塑性、自然转化能力和致病性。
