Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore.
Genome Biol Evol. 2013;5(5):807-18. doi: 10.1093/gbe/evt047.
The emergence of extreme-drug-resistant (EDR) bacterial strains in hospital and nonhospital clinical settings is a big and growing public health threat. Understanding the antibiotic resistance mechanisms at the genomic levels can facilitate the development of next-generation agents. Here, comparative genomics has been employed to analyze the rapid evolution of an EDR Acinetobacter baumannii clone from the intensive care unit (ICU) of Rigshospitalet at Copenhagen. Two resistant A. baumannii strains, 48055 and 53264, were sequentially isolated from two individuals who had been admitted to ICU within a 1-month interval. Multilocus sequence typing indicates that these two isolates belonged to ST208. The A. baumannii 53264 strain gained colistin resistance compared with the 48055 strain and became an EDR strain. Genome sequencing indicates that A. baumannii 53264 and 48055 have almost identical genomes-61 single-nucleotide polymorphisms (SNPs) were found between them. The A. baumannii 53264 strain was assembled into 130 contigs, with a total length of 3,976,592 bp with 38.93% GC content. The A. baumannii 48055 strain was assembled into 135 contigs, with a total length of 4,049,562 bp with 39.00% GC content. Genome comparisons showed that this A. baumannii clone is classified as an International clone II strain and has 94% synteny with the A. baumannii ACICU strain. The ResFinder server identified a total of 14 antibiotic resistance genes in the A. baumannii clone. Proteomic analyses revealed that a putative porin protein was down-regulated when A. baumannii 53264 was exposed to antimicrobials, which may reduce the entry of antibiotics into the bacterial cell.
在医院和非医院临床环境中出现的极端耐药(EDR)细菌菌株是一个日益严重的公共卫生威胁。了解基因组水平的抗生素耐药机制可以促进下一代药物的开发。在这里,我们采用比较基因组学方法分析了来自哥本哈根 Rigshospitalet 重症监护病房(ICU)的 EDR 鲍曼不动杆菌克隆的快速进化。先后从在 1 个月内入住 ICU 的 2 名个体中分离出 2 株耐药鲍曼不动杆菌 48055 和 53264。多位点序列分型表明,这两株分离株属于 ST208。与 48055 株相比,鲍曼不动杆菌 53264 株获得了多粘菌素耐药性,并成为 EDR 菌株。基因组测序表明,鲍曼不动杆菌 53264 和 48055 的基因组几乎完全相同-它们之间发现了 61 个单核苷酸多态性(SNP)。鲍曼不动杆菌 53264 株被组装成 130 个contigs,总长度为 3976592bp,GC 含量为 38.93%。鲍曼不动杆菌 48055 株被组装成 135 个 contigs,总长度为 4049562bp,GC 含量为 39.00%。基因组比较表明,该鲍曼不动杆菌克隆被归类为国际克隆 II 株,与鲍曼不动杆菌 ACICU 株具有 94%的同线性。ResFinder 服务器总共在鲍曼不动杆菌克隆中鉴定出 14 个抗生素耐药基因。蛋白质组学分析显示,当鲍曼不动杆菌 53264 暴露于抗生素时,一种假定的孔蛋白被下调,这可能会减少抗生素进入细菌细胞。