title: Genomic epidemiology of Klebsiella pneumoniae in Italy and novel insights into the origin and global evolution of its resistance to carbapenem antibiotics.
abstract: Klebsiella pneumoniae is at the forefront of antimicrobial resistance for Gram-negative pathogenic bacteria, as strains resistant to third-generation cephalosporins and carbapenems are widely reported. The worldwide diffusion of these strains is of great concern due to the high morbidity and mortality often associated with K. pneumoniae infections in nosocomial environments. We sequenced the genomes of 89 K. pneumoniae strains isolated in six Italian hospitals. Strains were selected based on antibiotypes, regardless of multilocus sequence type, to obtain a picture of the epidemiology of K. pneumoniae in Italy. Thirty-one strains were carbapenem-resistant K. pneumoniae carbapenemase producers, 29 were resistant to third-generation cephalosporins, and 29 were susceptible to the aforementioned antibiotics. The genomes were compared to all of the sequences available in the databases, obtaining a data set of 319 genomes spanning the known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global data set allowed us to construct a whole-species phylogeny, to detect patterns of antibiotic resistance distribution, and to date the differentiation between specific clades of interest. Finally, we detected an ∼ 1.3-Mb recombination that characterizes all of the isolates of clonal complex 258, the most widespread carbapenem-resistant group of K. pneumoniae. The evolution of this complex was modeled, dating the newly detected and the previously reported recombination events. The present study contributes to the understanding of K. pneumoniae evolution, providing novel insights into its global genomic characteristics and drawing a dated epidemiological scenario for this pathogen in Italy.
authors.affiliation: Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Dipartimento di Scienze Veterinarie e Sanità Pubblica (DIVET), Università degli Studi di Milano, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gaiarsa
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica (DIVET), Università degli Studi di Milano, Milan, Italy Dipartimento di Biologia e Biotecnologie, Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Comandatore
authors.affiliation: Unit of Clinical Microbiology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gaibani
authors.affiliation: Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Biometric and Medical Statistics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Corbella
authors.affiliation: Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dalla Valle
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica (DIVET), Università degli Studi di Milano, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Epis
authors.affiliation: Sezione Diagnostica di Parma, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna (IZSLER), Parma, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Scaltriti
authors.affiliation: Clinical Microbiology Laboratory, IRCCS Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Carretto
authors.affiliation: Microbiology Institute, AO Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Farina
authors.affiliation: Dipartimento di Diagnostica di Laboratorio e Trasfusionale, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Labonia
authors.affiliation: Unit of Clinical Microbiology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Landini
authors.affiliation: Sezione Diagnostica di Parma, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna (IZSLER), Parma, Italy.
authors.forename: Stefano
authors.identifier: http://orcid.org/0000-0002-4823-3562
authors.initials: S
authors.lastname: Pongolini
authors.affiliation: Unit of Clinical Microbiology, The Greater Romagna Area-Hub Laboratory, Pievesestina, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sambri
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica (DIVET), Università degli Studi di Milano, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bandi
authors.affiliation: Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Marone
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università degli Studi di Pavia, Pavia, Italy davide.sassera@unipv.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Sassera
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015373:Bacterial Typing Techniques; D001483:Base Sequence; D015780:Carbapenems / Q000627:therapeutic use*; D003428:Cross Infection / Q000382:microbiology; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004269:DNA, Bacterial; D001618:beta-Lactamases