Genetic Factors Related to the Widespread Dissemination of ST11 Extensively Drug-Resistant Carbapenemase-Producing Klebsiella pneumoniae Strains Within Hospital
Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses significant clinical challenges due to its extensively drug-resistant (XDR) phenotype, which is associated with high morbidity and mortality in hospital-acquired infections. Among the various sequence types (STs) of CP-Kp, ST11 is the most dominant clone carrying the blaKPC-2 gene in China. This study aimed to explore the genetic factors contributing to the widespread dissemination of ST11 XDR CP-Kp strains within the intensive care unit (ICU) of a Chinese tertiary hospital.
The study retrospectively analyzed six ST11 XDR CP-Kp strains isolated from patients in the ICU between May and December 2014. These strains were identified through minimum inhibitory concentration (MIC) testing, polymerase chain reaction (PCR), and pyrosequencing. Additionally, three multi-drug resistant (MDR) and four susceptible (S) K. pneumoniae strains were included for comparative analysis. Whole genome sequencing (WGS) was performed using the single-molecule real-time (SMRT) method, and comprehensive structural and functional analyses were conducted to identify the genomic characteristics unique to the ST11 XDR CP-Kp strains.
The six ST11 XDR CP-Kp strains were found to have spread within the ICU, with two distinct clones identified. Phylogenetic analysis revealed that these strains were highly similar, with a low number of core single-nucleotide polymorphisms (SNPs) among them. The strains exhibited variations in chromosome size, antimicrobial resistance phenotypes, and the distribution of antimicrobial resistance genes (ARGs). Notably, all six strains carried the blaKPC-2 gene on IncFII plasmids, which are known to be prominent carriers of ARGs.
Comparative genomics analysis revealed that the ST11 XDR CP-Kp strains had larger genomes and a higher number of predicted coding sequences (CDSs) compared to the MDR and S strains. Functional annotation based on Clusters of Orthologous Groups (COG) classifications showed that the XDR strains had a higher proportion of genes involved in information storage and processing, particularly those related to mobile genetic elements (MGEs) such as transposons and prophages.
The study identified 11 large-scale genetic regions unique to the ST11 XDR CP-Kp strains, which were associated with MGEs. These regions included transposons, integrons, prophages, genomic islands, and integrative and conjugative elements (ICEs). Three of these regions were located on plasmids, while eight were on chromosomes. Five of these MGEs carried ARGs, and eight carried adaptation-associated genes. A novel blaKPC-2-bearing transposon, designated DDTn1721-blaKPC-2, was identified in all six ST11 XDR CP-Kp strains. This transposon is likely a truncated version of the previously described DTn1721-blaKPC-2, with IS903D and ISKpn8 elements flanking the blaKPC-2 gene.
The MGEs identified in the ST11 XDR CP-Kp strains are known to play a crucial role in the horizontal transfer of ARGs and adaptation-associated genes. The presence of these MGEs may contribute to the formidable adaptability and widespread dissemination of these strains within the hospital environment. For instance, the IncFII plasmids carrying blaKPC-2 are highly transmissible and have been found in various Enterobacteriaceae species, facilitating the spread of carbapenem resistance.
In addition to ARGs, the study identified several adaptation-associated genes carried by MGEs in the ST11 XDR CP-Kp strains. These genes are involved in various cellular processes, including DNA repair, cell wall/membrane/envelope biosynthesis, defense mechanisms, and respiratory chain function. For example, the ICE_F1 element carried genes encoding LytM and LytR, which are involved in cell wall biosynthesis and biofilm formation, potentially enhancing the virulence and antibiotic resistance of the strains.
The dissemination of ST11 XDR CP-Kp strains within the ICU highlights the importance of infection control measures in healthcare settings. The study underscores the role of MGEs in the evolution and spread of antibiotic resistance, particularly in high-risk clones like ST11. The identification of unique genetic elements in these strains provides valuable insights into the mechanisms underlying their success and may inform the development of novel therapeutic targets.
In conclusion, the widespread dissemination of ST11 XDR CP-Kp strains within the hospital is driven by a combination of clonal spread and horizontal gene transfer mediated by MGEs. The presence of unique MGEs carrying ARGs and adaptation-associated genes contributes to the strains’ adaptability and persistence in the hospital environment. This study provides a comprehensive understanding of the genetic factors associated with the success of ST11 XDR CP-Kp strains and emphasizes the need for continued surveillance and research to combat the spread of these highly resistant pathogens.
doi.org/10.1097/CM9.0000000000001101
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