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

Abstract

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 Tn4401-like (e.g., Tn4401a, Tn4401b, and IS6100_ΔTn4401b) and Tn7247-like (e.g., IS26_ΔTn7247_IS26, IS6100_ΔTn7247) 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. Tn4401-like elements were predominantly found in the Americas and were chromosome-located in 23.3 % (131/562) of the cases. In contrast, Tn7247-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 Tn4401, as well as chimeric structures formed by IS26/IS6100 and truncated Tn7247, played a major role in the dissemination of bla_KPC among clinical CRPA isolates.