Characterisation of genetic context of blaKPC in Pseudomonas aeruginosa

Xiao Ming Chen¹Ting Ting Deng¹Bin Xiao Li²Cheng Run Zhou³Shu Zhang Gao¹Die Zhou¹Qiang Jian Zhu¹Jie Jing Li¹Xin Chen³Ling Min Wang^1*Rui Zhang^2*Qiang Zhou^1*

• ¹Guangzhou Medical University Second Affiliated Hospital, Guangzhou, China
• ²Zhuhai City People's Hospital, Zhuhai, China
• ³Foshan University, Foshan, China

The spread of blaKPC-harboring Pseudomonas aeruginosa (KPC-PA) poses a significant public health threat. Here we identified a carbapenem-resistant P. aeruginosa (PAE3) from a patient with pneumonia infection. The resistance phenotype was analyzed by the broth microdilution method. Whole-genome sequencing was performed to sequence type (ST), resistance genes, plasmid replicon and the genetic environment of the blaKPC-2 gene. The other 75 PA isolates with chromosome- or plasmid-borne blaKPC gene were incorporated into analyzing the mobilized characterization of blaKPC 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 blaKPC-2 gene that is located within a Tn1721-like transposon in south China. 76 KPC-PA strains from 7 countries, representing 6 distinct blaKPC variants—blaKPC-2, blaKPC-3, blaKPC-33, blaKPC-87, blaKPC-90 and blaKPC-113—with the majority located within transposons such as Tn1403, Tn1721, Tn4401, or Tn6296-like elements. 63 blaKPC-positive plasmids evolved different phylogenetic clades in China and other countries, indicating clonal transmission and regional evolution. The dissemination of blaKPC is primarily observed in three distinct forms in ST463 KPC-PA in China: (1) plasmid-mediated transfer associated with Tn6296-like transposon; (2) Tn1721 and the IS26-ISKpn27-blaKPC-2-ISKpn6 structural arrangement that is integrated into both plasmid and chromosome. In contrast, the Tn4401 is commonly observed in Europe and the United States that predominantly emerging in ST235. This study represents the valuable systematic classification of the transposons associated with blaKPC acquisition and offers new insights into the mobilized genetic platforms that contributed to the global dissemination of carbapenem resistance in PA.