Characterization of genetic context of blaKPC in Pseudomonas aeruginosa

The rising prevalence of <i>bla</i> _KPC-harboring <i>Pseudomonas aeruginosa</i> (KPC-PA) is a significant threat to public health. In the study, we identified a carbapenem-resistant <i>P. aeruginosa</i> (CRPA; PAE3) from a patient with pneumonia infection. The resistance phenotype was analyzed using the broth microdilution method. Whole-genome sequencing was performed to sequence type (ST), resistance genes, plasmid replicon, and the genetic environment of the <i>bla</i> _KPC-2 gene. The other 75 <i>Pseudomonas aeruginosa</i> (PA) isolates with chromosome- or plasmid-borne <i>bla</i> _KPC gene were used to analyze the mobilized characterization of <i>bla</i> _KPC gene in PA from a global perspective. The result revealed PAE3 belonged to ST463 and exhibited multidrug resistance, which is the first report of PA harboring a chromosome-borne <i>bla</i> _KPC-2 gene located within a Tn<i>1721</i>-like transposon in South China. In total, 76 KPC-PA strains were identified from 7 countries, representing 6 distinct <i>bla</i> _KPC variants-<i>bla</i> _KPC-2, <i>bla</i> _KPC-3, <i>bla</i> _KPC-33, <i>bla</i> _KPC-87, <i>bla</i> _KPC-90, and <i>bla</i> _KPC-113-with the majority located within transposons such as Tn<i>1403</i>, Tn<i>1721</i>, Tn<i>4401</i>, or Tn<i>6296</i>-like elements. A total of 63 <i>bla</i> _KPC-positive plasmids evolved into different phylogenetic clades in China and other countries, indicating clonal transmission and regional evolution. The dissemination of <i>bla</i> _KPC is primarily observed in three distinct forms in ST463 KPC-PA in China: (1) plasmid-mediated transfer associated with Tn<i>6296</i>-like transposon; (2) Tn<i>1721,</i> and (3) the IS<i>26</i>-IS<i>Kpn27</i>-<i>bla</i> _KPC-2-IS<i>Kpn6</i> structural arrangement, which is integrated into both plasmid and chromosome. In contrast, Tn<i>4401</i> is commonly observed in Europe and the United States, predominantly emerging in ST235. This study represents the valuable systematic classification of the transposons associated with the spread of <i>bla</i> _KPC and offers new insights into the mobilized genetic platforms that contributed to the global dissemination of carbapenem resistance in PA.