title: Phylogeny, resistome and mobile genetic elements of emergent OXA-48 and OXA-245 Klebsiella pneumoniae clones circulating in Spain.
abstract: OBJECTIVE
  The global emergence of OXA-48-producing Klebsiella pneumoniae clones is a significant threat to public health. We used WGS and phylogenetic analysis of Spanish isolates to investigate the population structure of blaOXA-48-like-expressing K. pneumoniae ST11 and ST405 and to determine the distribution of resistance genes and plasmids encoding blaOXA-48-like carbapenemases.
  
  
  METHODS
  SNPs identified in whole-genome sequences were used to reconstruct phylogenetic trees, identify resistance determinants and de novo assemble the genomes of 105 blaOXA-48-like-expressing K. pneumoniae isolates.
  
  
  RESULTS
  Genome variation was generally lower in outbreak-associated isolates compared with those associated with sporadic infections. The relatively limited variation observed within the outbreak-associated isolates was on average 7-10 SNPs per outbreak. Of 24 isolates from suspected sporadic infections, 7 were very closely related to isolates causing hospital outbreaks and 17 were more diverse and therefore probably true sporadic cases. On average, 14 resistance genes were identified per isolate. The 17 ST405 isolates from sporadic cases of infection had four distinct resistance gene profiles, while the resistance gene profile differed in all ST11 isolates from sporadic cases. Sequence analysis of 94 IncL/M plasmids carrying blaOXA-48-like genes revealed an average of two SNP differences, indicating a conserved plasmid clade.
  
  
  CONCLUSIONS
  Whole-genome sequence analysis enabled the discrimination of outbreak and sporadic isolates. Significant inter-regional spread within Spain of highly related isolates was evident for both ST11 and ST405 K. pneumoniae. IncL/M plasmids carrying blaOXA-48-like carbapenemase genes were highly conserved geographically and across the outbreaks, sporadic cases and clones.
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain mperezv@isciii.es.
authors.forename: María
authors.initials: M
authors.lastname: Pérez-Vázquez
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Oteo
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Silvia
authors.initials: S
authors.lastname: García-Cobos
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Aracil
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Laboratorio de Microbiología, Hospital Parc Taulí, Sabadell, Barcelona, Spain.
authors.forename: Dionisia
authors.initials: D
authors.lastname: Fontanals
authors.affiliation: Servicio de Microbiología, Hospital Carlos Haya, Málaga, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Hernández
authors.affiliation: Servicio de Microbiología, Hospital de Guadalajara, Guadalajara, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Solís
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Campos
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK The Institute of Food Research, Colney, Norwich, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D003428:Cross Infection; D004269:DNA, Bacterial / Q000235:genetics; D004196:Disease Outbreaks; D014644:Genetic Variation; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D017720:Molecular Epidemiology; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D013030:Spain / Q000453:epidemiology; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D001618:beta-Lactamases; C063912:carbapenemase