title: High-Resolution Analysis by Whole-Genome Sequencing of an International Lineage (Sequence Type 111) of Pseudomonas aeruginosa Associated with Metallo-Carbapenemases in the United Kingdom.
abstract: Whole-genome sequencing (WGS) was carried out on 87 isolates of sequence type 111 (ST-111) of Pseudomonas aeruginosa collected between 2005 and 2014 from 65 patients and 12 environmental isolates from 24 hospital laboratories across the United Kingdom on an Illumina HiSeq instrument. Most isolates (73) carried VIM-2, but others carried IMP-1 or IMP-13 (5) or NDM-1 (1); one isolate had VIM-2 and IMP-18, and 7 carried no metallo-beta-lactamase (MBL) gene. Single nucleotide polymorphism analysis divided the isolates into distinct clusters; the NDM-1 isolate was an outlier, and the IMP isolates and 6/7 MBL-negative isolates clustered separately from the main set of 73 VIM-2 isolates. Within the VIM-2 set, there were at least 3 distinct clusters, including a tightly clustered set of isolates from 3 hospital laboratories consistent with an outbreak from a single introduction that was quickly brought under control and a much broader set dominated by isolates from a long-running outbreak in a London hospital likely seeded from an environmental source, requiring different control measures; isolates from 7 other hospital laboratories in London and southeast England were also included. Bayesian evolutionary analysis indicated that all the isolates shared a common ancestor dating back ∼50 years (1960s), with the main VIM-2 set separating approximately 20 to 30 years ago. Accessory gene profiling revealed blocks of genes associated with particular clusters, with some having high similarity (≥95%) to bacteriophage genes. WGS of widely found international lineages such as ST-111 provides the necessary resolution to inform epidemiological investigations and intervention policies.
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, Colindale, London, United Kingdom jane.turton@phe.gov.uk.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Turton
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, Colindale, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Wright
authors.affiliation: Infectious Disease Informatics, Public Health England, Colindale, London, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Underwood
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, London, United Kingdom.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Witney
authors.affiliation: Genomic Services and Development Unit, Public Health England, Colindale, London, United Kingdom.
authors.forename: Yuen-Ting
authors.initials: YT
authors.lastname: Chan
authors.affiliation: Infectious Disease Informatics, Public Health England, Colindale, London, United Kingdom.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Shahib
authors.affiliation: Genomic Services and Development Unit, Public Health England, Colindale, London, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Arnold
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, Colindale, London, United Kingdom.
authors.forename: Michel
authors.initials: M
authors.lastname: Doumith
authors.affiliation: Public Health Laboratory London, Whitechapel, London, United Kingdom.
authors.forename: Bharat
authors.initials: B
authors.lastname: Patel
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, London, United Kingdom Department of Microbiology, St George's Healthcare NHS Trust, London, United Kingdom.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Planche
authors.affiliation: Infectious Disease Informatics, Public Health England, Colindale, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Green
authors.affiliation: Public Health Laboratory London, Whitechapel, London, United Kingdom Institute of Infection and Immunity, St. George's University of London, London, United Kingdom Department of Microbiology, St George's Healthcare NHS Trust, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Holliman
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, Colindale, London, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Woodford
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D016000:Cluster Analysis; D004196:Disease Outbreaks; D004783:Environmental Microbiology; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011552:Pseudomonas Infections / Q000453:epidemiology / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000145:classification* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D006113:United Kingdom / Q000453:epidemiology; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase