Genomic epidemiology of Klebsiella pneumoniae: the Italian scenario, and novel insights into the origin and global evolution of resistance to carbapenem antibiotics

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, also 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; 29 were susceptible to the aforementioned antibiotics. The genomes were compared with all the sequences available in the databases, obtaining a dataset of 319 genomes spanning the known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global dataset 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 a ∼1.3 Mb recombination that characterizes all the isolates of Clonal Complex 258, the most widespread carbapenem-resistant group of K. pneumoniae. The evolution of this complex was modelled, 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.