Emergence of carbapenem-resistant Klebsiella pneumoniae harbouring bla OXA-48-like genes in China

Abstract

<i>Klebsiella pneumoniae</i> strains carrying OXA-48-like carbapenemases are increasingly prevalent across the globe. There is thus an urgent need to better understand the mechanisms that underpin the dissemination of <i>bla</i> _OXA-48-like carbapenemases. To this end, four ertapenem-resistant <i>K. pneumoniae</i> isolates producing OXA-48-like carbapenemases were isolated from two patients. Genome sequencing revealed that one sequence type (ST) 17 isolate carried <i>bla</i> _OXA-181, whilst three isolates from a single patient, two ST76 and one ST15, carried <i>bla</i> _OXA-232. The 50514 bp <i>bla</i> _OXA-181-harbouring plasmid, pOXA-181_YML0508, was X3-type with a conjugation frequency to <i>Escherichia coli</i> of 1.94×10^-4 transconjugants per donor. The <i>bla</i> _OXA-232 gene was located on a 6141 bp ColKP3-type plasmid, pOXA-232_WSD, that was identical in the ST76 and ST15 <i>K. pneumoniae</i> isolates. This plasmid could be transferred from <i>K. pneumoniae</i> to <i>E. coli</i> at low frequency, 8.13×10^-6 transconjugants per donor. Comparative analysis revealed that the X3 plasmid acquired the <i>bla</i> _OXA-48-like gene via IS<i>3000</i>-mediated co-integration of the ColKP3-type plasmid. Our study highlights how plasmid integration and rearrangements can contribute to the spread of <i>bla</i> _OXA-48-like genes, which provides important clues for clinical prevention of the dissemination of <i>K. pneumoniae</i> strains carrying <i>bla</i> _OXA-48-like carbapenemases.