Tn4401/Tn7247 transposon-derived structures driving the cross-transmission of blaKPC among plasmids and chromosomes in clinical carbapenem-resistant Pseudomonas aeruginosa

• A significant proportion (∼11%) of bla KPC genes were chromosome-integrated in P. aeruginosa . • Tn 4401 /Tn 7247 -like structures were the major transposons mobilizing bla KPC . • Tn 4401 - and Tn 7247 -like structures differed in geographic distribution and plasmid/chromosome localization. • IS 26 and IS 6100 formed prevalent chimeric structures with truncated transposons to mobilize bla KPC . • Integrative mobilizable elements (IMEs) facilitated inter-cellular transfer of chromosomal bla KPC . Carbapenem-resistant Pseudomonas aeruginosa (CRPA) harboring bla KPC gene poses a formidable clinical challenge. However, the distribution and horizontal transfer mechanisms of bla KPC in CRPA have not been systematically elucidated. We collected 1,063 clinical CRPA isolates from 30 provincial administrative regions in China, among which 79 carried bla KPC . In addition, 35,607 public P.aeruginosa genome sequences were acquired, among which 1,141 harbored bla KPC . Detailed analysis of the bla KPC genetic contexts in the combined dataset of the 1,220 P.aeruginosa genomes revealed that 10.4% (174/1,680) of the bla KPC genes were located on chromosomes which were primarily identified in ST282 isolates (79/174, 45.4%), mostly collected in the United States. In contrast, plasmid-located bla KPC genes were predominantly detected in ST463 isolates, mainly collected in China. Furthermore, our analysis frequently identified Tn 4401 -like (e.g., Tn 4401a , Tn 4401b , and IS 6100 _ΔTn 4401b ) and Tn 7247 -like (e.g., IS 26 _ΔTn 7247 _IS 26 , IS 6100 _ΔTn 7247 ) transposable elements carrying intact bla KPC , accounting for 36% (562/1,559) and 59.7% (930/1,559) of the cases, respectively. These two elements exhibited strikingly distinct geographic distribution and chromosome/plasmid localization preference. Tn 4401 -like elements were predominantly found in the Americas and were chromosome-located in 23.3% (131/562) of the cases. In contrast, Tn 7247 -like elements were prevalent in China and the chromosome-located proportion was only 3.5% (33/930). Among the chromosome-located bla KPC genes, 13/174 were identified within integrative and mobilizable elements (IMEs). These findings offered new insights into the horizontal transmission mechanisms of bla KPC in CRPA, indicating that complete Tn 4401 , as well as chimeric structures formed by IS 26/ IS 6100 and truncated Tn 7247 , played a major role in the dissemination of bla KPC among clinical CRPA isolates.