Genetic factors related to the widespread dissemination of ST11 extensively drug-resistant carbapenemase-producing Klebsiella pneumoniae strains within hospital

Background:Carbapenemase-producing Klebsiella pneumoniae(CP-Kp)poses distinct clinical challenges due to extensively drug resistant(XDR)phenotype,and sequence type(ST)11 is the most dominant blaKPC-2-bearing CP-Kp clone in China.The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit(ICU)of a Chinese tertiary hospital.Methods:Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination,polymerase chain reaction,and pyrosequencing.The six ST11 XDR CP-Kp,as well as three multi-drug resistant(MDR)and four susceptible strains,were sequenced using single-molecule real-time method.Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains.Results:We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital.Functionally,genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains,especially genes correlative with mobile genetic elements(MGEs)such as transposons and prophages.Structurally,eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons,integrons,prophages,genomic islands,and integrative and conjugative elements.Three of them were located on plasmids and eight on chromosomes;five of them were with antimicrobial resistance genes and eight with adaptation associated genes.Notably,a new blaKPC-2-bearingΔΔTn1721-blaKPC-2 transposon,probably transposed and truncated fromΔTn1721-blaKPC-2 by IS903D and ISKpn8,was identified in all six ST11 XDR CP-Kp strains.Conclusion:Our findings suggested that together with clonal spread,MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability,which facilitated their widespread dissemination in hospital.