title: Genomic Analysis of the Emergence and Rapid Global Dissemination of the Clonal Group 258 Klebsiella pneumoniae Pandemic.
abstract: Multidrug-resistant Klebsiella pneumoniae producing the KPC carbapenemase have rapidly spread throughout the world, causing severe healthcare-associated infections with limited antimicrobial treatment options. Dissemination of KPC-producing K. pneumoniae is largely attributed to expansion of a single dominant strain, ST258. In this study, we explore phylogenetic relationships and evolution within ST258 and its clonal group, CG258, using whole genome sequence analysis of 167 isolates from 20 countries collected over 17 years. Our results show a common ST258 ancestor emerged from its diverse parental clonal group around 1995 and likely acquired blaKPC prior to dissemination. Over the past two decades, ST258 has remained highly clonal despite diversity in accessory elements and divergence in the capsule polysaccharide synthesis locus. Apart from the large recombination event that gave rise to ST258, few mutations set it apart from its clonal group. However, one mutation occurs in a global transcription regulator. Characterization of outer membrane protein sequences revealed a profile in ST258 that includes a truncated OmpK35 and modified OmpK37. Our work illuminates potential genomic contributors to the pathogenic success of ST258, helps us better understand the global dissemination of this strain, and identifies genetic markers unique to ST258.
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Jolene R
authors.initials: JR
authors.lastname: Bowers
authors.affiliation: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Brandon
authors.initials: B
authors.lastname: Kitchel
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Driebe
authors.affiliation: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: MacCannell
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Chandler
authors.initials: C
authors.lastname: Roe
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Darrin
authors.initials: D
authors.lastname: Lemmer
authors.affiliation: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Tom
authors.initials: T
authors.lastname: de Man
authors.affiliation: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: J Kamile
authors.initials: JK
authors.lastname: Rasheed
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Engelthaler
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
authors.affiliation: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Brandi M
authors.initials: BM
authors.lastname: Limbago
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D006801:Humans; D007711:Klebsiella pneumoniae / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D008969:Molecular Sequence Data; D009154:Mutation; D058873:Pandemics; D010802:Phylogeny; D011014:Pneumonia / Q000453:epidemiology / Q000382:microbiology*; D018272:Porins / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C118791:OmpK37 protein, Klebsiella pneumoniae; D018272:Porins