title: Evolution and Epidemiology of Multidrug-ResistantKlebsiella pneumoniaein the United Kingdom and Ireland.
abstract: Klebsiella pneumoniaeis a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades. The emergence and global expansion of hypervirulent and multidrug-resistant (MDR) clones ofK. pneumoniaehave been increasingly reported in community-acquired and nosocomial infections. Despite this, the population genomics and epidemiology of MDRK. pneumoniaeat the national level are still poorly understood. To obtain insights into these, we analyzed a systematic large-scale collection of invasive MDRK. pneumoniaeisolates from hospitals across the United Kingdom and Ireland. Using whole-genome phylogenetic analysis, we placed these in the context of previously sequencedK. pneumoniaepopulations from geographically diverse countries and identified their virulence and drug resistance determinants. Our results demonstrate that United Kingdom and Ireland MDR isolates are a highly diverse population drawn from across the global phylogenetic tree ofK. pneumoniaeand represent multiple recent international introductions that are mainly from Europe but in some cases from more distant countries. In addition, we identified novel genetic determinants underlying resistance to beta-lactams, gentamicin, ciprofloxacin, and tetracyclines, indicating that both increased virulence and resistance have emerged independently multiple times throughout the population. Our data show that MDRK. pneumoniaeisolates in the United Kingdom and Ireland have multiple distinct origins and appear to be part of a globally circulatingK. pneumoniaepopulation.IMPORTANCEKlebsiella pneumoniaeis a major human pathogen that has been implicated in infections in healthcare settings over the past few decades. Antimicrobial treatment ofK. pneumoniaeinfections has become increasingly difficult as a consequence of the emergence and spread of strains that are resistant to multiple antimicrobials. To better understand the spread of resistantK. pneumoniae, we studied the genomes of a large-scale population of extensively antimicrobial-resistantK. pneumoniaein the United Kingdom and Ireland by utilizing the fine resolution that whole-genome sequencing of pathogen genomes provides. Our results indicate that theK. pneumoniaepopulation is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years. In addition, we found evidence that some strains have acquired antimicrobial resistance genes independently, presumably in response to antimicrobial treatment.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Danesh
authors.initials: D
authors.lastname: Moradigaravand
authors.affiliation: British Society for Antimicrobial Chemotherapy, Birmingham, United Kingdom.
authors.forename: Veronique
authors.initials: V
authors.lastname: Martin
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.|Department of Medicine, University of Cambridge, Cambridge, United Kingdom.|London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom parkhill@sanger.ac.uk.
authors.forename: Julian
authors.identifier: 0000-0002-7069-5958
authors.initials: J
authors.lastname: Parkhill
mesh_terms: D024901:Drug Resistance, Multiple, Bacterial; D014644:Genetic Variation; D006761:Hospitals; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D007710:Klebsiella Infections / Q000453:epidemiology* / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D017720:Molecular Epidemiology; D058889:Molecular Typing; D010802:Phylogeny; D006113:United Kingdom / Q000453:epidemiology