Characteristic of KPC-14, a KPC Variant Conferring Resistance to Ceftazidime-Avibactam in the Extensively Drug-resistant ST463 Pseudomonas aeruginosa Clinical Isolate

We studied two KPC-14 variants from clinical Pseudomonas aeruginosa isolates, C137 and C159, to better understand genomic diversity, mechanisms, and genes that confer antibiotic resistance and pathogenicity. C137 and C159, a sequence type 463 ExoU-positive multidrug-resistant strain, were concurrently resistant to carbapenems and ceftazidime-avibactam (CZA). Both strains possessed five intrinsic antimicrobial resistance genes (fosA, catB7, crpP, blaPAO, and a blaOXA-486 variant), as well as the blaKPC-14 gene in the chromosome. In strain C137, blaKPC-14 gene was situated on the plasmid pC137. KPC-14-harbouring transformants of pC137 exhibited resistance to CZA and restored sensitivity to carbapenems, signifying a "see-saw" effect. Both strains demonstrated the expression of the blaKPC-14 gene, concurrent inactivation of the outer membrane protein OprD, overexpression of the efflux pump MexX, and a pronounced capacity for biofilm formation. The genomic environment of KPC-14 consisted of IS26/IS26/TnpR_Tn3/ISKpn27/ISKpn6/IS26, which was classified as pseudo-compound transposons (PCTs). Plasmid pC137 closely resembled the previously described plasmid p94, which possesses the same genomic architecture, implying that IS26-mediated PCTs may store a variety of resistance genes, including blaKPC-2 and KPC variants, and were currently disseminating in the region. The KPC-14 variant presents significant challenges for clinical treatment. The blaKPC-14 gene, carried by the PCTs, was integrated into the chromosome, exhibiting stability throughout bacterial inheritance. Our research highlights the necessity for improved clinical surveillance of Klebsiella pneumoniae carbapenemase-producing P. aeruginosa.