Analysis of Serial Isolates of mcr-1 -Positive Escherichia coli Reveals a Highly Active IS Apl1 Transposon

The emergence of a transferable colistin resistance gene ( mcr-1 ) is of global concern. The insertion sequence IS Apl1 is a key component in the mobilization of this gene, but its role remains poorly understood. Six Escherichia coli 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 mcr-1 as determined by real-time PCR, but two were negative. Two additional mcr-1 -negative E. coli 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 E. coli strain harboring mcr-1 and a second, unrelated, mcr-1 -negative ST-32 E. coli strain that emerged 2 weeks after hospitalization. Follow-up swabs taken 9 months later were negative for the ST-617 strain, but the mcr-1 -negative ST-32 strain was still present. mcr-1 was associated with a single copy of IS Apl1 , located on a 64.5-kb IncI2 plasmid that shared >95% homology with other mcr-1 IncI2 plasmids. IS Apl1 copy numbers ranged from 2 for the first isolate to 6 for the final isolate, but IS Apl1 movement was independent of mcr-1 . 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 Apl1 movement in serial clinical isolates and reveal that, under certain conditions, IS Apl1 is a highly active IS element whose movement may be detrimental to the host cell.