Klebsiella pneumoniae blaKPC-3 nosocomial epidemic: Bayesian and evolutionary analysis

• Published in: Infection, genetics and evolution genetics and evolution, 2016-12, Vol.46, p.85-93
• Main Authors: Angeletti, Silvia, Presti, Alessandra Lo, Cella, Eleonora, Fogolari, Marta, De Florio, Lucia, Dedej, Etleva, Blasi, Aletheia, Milano, Teresa, Pascarella, Stefano, Incalzi, Raffaele Antonelli, Coppola, Roberto, Dicuonzo, Giordano, Ciccozzi, Massimo
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - classification; Bacterial Proteins - genetics; Bayes Theorem; Bayesian analysis; beta-Lactamases - classification; beta-Lactamases - genetics; blaKPC-3 gene; Cross Infection - epidemiology; Cross Infection - microbiology; DNA, Bacterial - analysis; DNA, Bacterial - genetics; Epidemics - statistics & numerical data; Evolution, Molecular; Evolutionary analysis; Humans; Italy - epidemiology; K. pneumoniae; Klebsiella Infections - epidemiology; Klebsiella Infections - microbiology; Klebsiella pneumoniae - classification; Klebsiella pneumoniae - genetics; Molecular Epidemiology; Phylogeny
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2016.10.031

K. pneumoniae isolates carrying blaKPC-3 gene were collected to perform Bayesian phylogenetic and selective pressure analysis and to apply homology modeling to the KPC-3 protein. A dataset of 44 blakpc-3 gene sequences from clinical isolates of K. pneumoniae was used for Bayesian phylogenetic, selective pressure analysis and homology modeling. The mean evolutionary rate for blakpc-3 gene was 2.67×10−3 substitution/site/year (95% HPD: 3.4×10−4–5.59×10–3). The root of the Bayesian tree dated back to the year 2011 (95% HPD: 2007–2012). Two main clades (I and II) were identified. The population dynamics analysis showed an exponential growth from 2011 to 2013 and the reaching of a plateau. The phylogeographic reconstruction showed that the root of the tree had a probable common ancestor in the general surgery ward. Selective pressure analysis revealed twelve positively selected sites. Structural analysis of KPC-3 protein predicted that the amino acid mutations are destabilizing for the protein and could alter the substrate specificity. Phylogenetic analysis and homology modeling of blaKPC-3 gene could represent a useful tool to follow KPC spread in nosocomial setting and to evidence amino acid substitutions altering the substrate specificity. •Bayesian phylogenetic and selective pressure analysis of blakpc type 3 gene to follow the spread of K. pneumoniae clinical isolates in nosocomial setting.•Homology modeling applied to the KPC-3 protein to evidence the influence of amino acid substitutions on the protein structure and substrate specificity.•The evolutionary rate, the time-scaled phylogeny, the population dynamics analysis and the phylogeography.•blaKPC gene can be applied to improve the epidemiological surveillance of antimicrobial resistance genes.