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

摘要

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 bla(kpc)-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 bla(kpc)-3 gene was 2.67 x 10(-3) substitution/site/year (95% HPD: 3.4 x 10(-4)-5.59 x 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. (C) 2016 Elsevier B.V. All rights reserved.