First genomic insights into carbapenem-resistant Klebsiella pneumoniae from Malaysia

OBJECTIVES: Despite the increasing report of carbapenem-resistant Enterobacteriaceae in Malaysia, genomic resource for carbapenem-resistant clinical strains of Klebsiella pneumoniae remains unavailable. In this study, we aim to fill in this gap by sequencing the genomes of multiple carbapenem-resistant K. pneumoniae strains from Malaysia in addition to identifying the genetic basis for their resistance. METHODS: Illumina whole-genome sequencing was performed on eight carbapenem-resistant Klebsiella pneumoniae isolated from a Malaysian hospital. Genetic diversity was inferred from the assembled genomes based on in-silico multi locus sequence typing (MLST). In addition, plasmid- and chromosome-derived contigs were predicted using machine learning approach. After genome annotation, genes associated with carbapenem resistance were identified based on similarity search against the ResFinder database. RESULTS: The eight K. pneumoniae isolates were grouped into six different sequence types, some of which were only represented by a single isolate in the MLST database. Genomic potential for carbapenem-resistance was attributed to the presence of plasmid-localized blaNDM (blaNDM-1/blaNDM-5) or blaKPC (blaKPC-2/blaKPC-6) in these sequenced strains. A majority of these carbapenem resistance genes were flanked by repetitive (transposase or integrase) sequences, suggesting their potential mobility. We also report the first blaKPC-6-harboring plasmid contig to be assembled for K. pneumoniae, the second for the genus Klebsiella. CONCLUSION: We report the first genomic resources for carbapenem-resistant K. pneumoniae from Malaysia. The high diversity of carbapenem resistance genes and sequence types uncovered from only 8 isolates from the same hospital is worrying and indicates an urgent need to improve the genomic surveillance of clinical K. pneumoniae in Malaysia.