Snesrud Erik, Ong Ana C, Corey Brendan, Kwak Yoon I, Clifford Robert, Gleeson Todd, Wood Shannon, Whitman Timothy J, Lesho Emil P, Hinkle Mary, McGann Patrick
Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Department of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.00056-17. Print 2017 May.
The emergence of a transferable colistin resistance gene () is of global concern. The insertion sequence IS is a key component in the mobilization of this gene, but its role remains poorly understood. Six isolates were cultured from the same patient over the course of 1 month in Germany and the United States after a brief hospitalization in Bahrain for an unconnected illness. Four carried as determined by real-time PCR, but two were negative. Two additional -negative isolates were collected during follow-up surveillance 9 months later. All isolates were analyzed by whole-genome sequencing (WGS). WGS revealed that the six initial isolates were composed of two distinct strains: an initial ST-617 strain harboring and a second, unrelated, -negative ST-32 strain that emerged 2 weeks after hospitalization. Follow-up swabs taken 9 months later were negative for the ST-617 strain, but the -negative ST-32 strain was still present. was associated with a single copy of IS, located on a 64.5-kb IncI2 plasmid that shared >95% homology with other IncI2 plasmids. IS copy numbers ranged from 2 for the first isolate to 6 for the final isolate, but IS movement was independent of Some movement was accompanied by gene disruption, including the loss of genes encoding proteins involved in stress responses, arginine catabolism, and l-arabinose utilization. These data represent the first comprehensive analysis of IS movement in serial clinical isolates and reveal that, under certain conditions, IS is a highly active IS element whose movement may be detrimental to the host cell.
可转移的黏菌素耐药基因()的出现引起了全球关注。插入序列IS是该基因转移的关键组成部分,但其作用仍知之甚少。在巴林因无关疾病短暂住院后,1个月内从德国和美国的同一患者身上培养出6株分离株。通过实时PCR检测,4株携带,但2株为阴性。9个月后的随访监测期间又收集到2株阴性分离株。所有分离株均通过全基因组测序(WGS)进行分析。WGS显示,最初的6株分离株由两种不同的菌株组成:一种是最初携带的ST-617菌株,另一种是住院2周后出现的无关的阴性ST-32菌株。9个月后采集的随访拭子中,ST-617菌株呈阴性,但阴性ST-32菌株仍然存在。与位于64.5 kb IncI2质粒上的单拷贝IS相关,该质粒与其他IncI2质粒具有>95%的同源性。IS拷贝数从第一株分离株的2个到最后一株分离株的6个不等,但IS的移动与无关。一些移动伴随着基因破坏,包括编码参与应激反应、精氨酸分解代谢和L-阿拉伯糖利用的蛋白质的基因丢失。这些数据代表了对连续临床分离株中IS移动的首次全面分析,并揭示在某些条件下,IS是一种高度活跃的IS元件,其移动可能对宿主细胞有害。