First genomic insights into carbapenem-resistant Klebsiella pneumoniae from Malaysia

Objectives: Despite the increasing reports of carbapenem-resistant Enterobacteriaceae in Malaysia, genomic resources for carbapenem-resistant clinical strains of Klebsiella pneumoniae (K. pneumoniae) remain unavailable. This study aimed to sequence the genomes of multiple carbapenem-resistant K. pneumoniae strains from Malaysia and to identify the genetic basis for their resistance.

Methods: Illumina whole genome sequencing was performed on eight carbapenem-resistant K. pneumoniae isolated from a Malaysian hospital. Genetic diversity was inferred from the assembled genomes based on in silico multilocus sequence typing (MLST). In addition, plasmid-derived and chromosome-derived contigs were predicted using the machine learning approach. After genome annotation, genes associated with carbapenem resistance were identified based on similarity searched against the ResFinder database.

Results: The eight K. pneumoniae isolates were grouped into six different sequence types, some of which were represented by a single isolate in the MLST database. Genomic potential for carbapenem-resistance was attributed to the presence of plasmid-localised bla_NDM (bla_NDM-1/bla_NDM-5) or bla_KPC (bla_KPC-2/bla_KPC-6) in these sequenced strains. The majority of these carbapenem resistance genes was flanked by repetitive (transposase or integrase) sequences, suggesting their potential mobility. This study also reported the first bla_KPC-6-harbouring plasmid contig to be assembled for K. pneumoniae, and the second for the genus Klebsiella.

Conclusion: This study reported the first genomic resources for carbapenem-resistant K. pneumoniae from Malaysia. The high diversity of carbapenem resistance genes and sequence types uncovered from eight isolates from the same hospital is worrying and indicates an urgent need to improve the genomic surveillance of clinical K. pneumoniae in Malaysia.