title: Analysis of Serial Isolates ofmcr-1-Positive Escherichia coli Reveals a Highly Active ISApl1Transposon.
abstract: The emergence of a transferable colistin resistance gene (mcr-1) is of global concern. The insertion sequence ISApl1is a key component in the mobilization of this gene, but its role remains poorly understood. SixEscherichia coliisolates 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 carriedmcr-1as determined by real-time PCR, but two were negative. Two additionalmcr-1-negativeE. coliisolates 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-617E. colistrain harboringmcr-1and a second, unrelated,mcr-1-negative ST-32E. colistrain that emerged 2 weeks after hospitalization. Follow-up swabs taken 9 months later were negative for the ST-617 strain, but themcr-1-negative ST-32 strain was still present.mcr-1was associated with a single copy of ISApl1, located on a 64.5-kb IncI2 plasmid that shared >95% homology with othermcr-1IncI2 plasmids. ISApl1copy numbers ranged from 2 for the first isolate to 6 for the final isolate, but ISApl1movement was independent ofmcr-1Some 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 ISApl1movement in serial clinical isolates and reveal that, under certain conditions, ISApl1is a highly active IS element whose movement may be detrimental to the host cell.
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Snesrud
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Ong
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Corey
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Yoon I
authors.initials: YI
authors.lastname: Kwak
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Clifford
authors.affiliation: Department of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Gleeson
authors.affiliation: Department of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Wood
authors.affiliation: Department of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Whitman
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Emil P
authors.initials: EP
authors.lastname: Lesho
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Hinkle
authors.affiliation: Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA patrick.t.mcgann4.civ@mail.mil.
authors.forename: Patrick
authors.initials: P
authors.lastname: McGann
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D003091:Colistin / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D029968:Escherichia coli Proteins / Q000235:genetics*; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; C000614037:MCR-1 protein, E coli; C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D003091:Colistin
keywords: colistin; mcr-1; plasmids