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

## TL;DR

This study shows how the blaKPC gene spreads in drug-resistant Pseudomonas aeruginosa through specific transposon structures, with differences in location and geography.

## Contribution

Identifies Tn4401/Tn7247 transposon-derived structures as key drivers of blaKPC dissemination in clinical Pseudomonas aeruginosa isolates.

## Key findings

- Approximately 11% of blaKPC genes were found integrated into chromosomes in P. aeruginosa.
- Tn4401- and Tn7247-like transposons showed distinct geographic and genomic localization patterns.
- Chimeric structures involving IS26 and IS6100 with truncated transposons were common in mobilizing blaKPC.

## Abstract

•A significant proportion (∼11 %) of blaKPC genes were chromosome-integrated in P. aeruginosa.•Tn4401/Tn7247-like structures were the major transposons mobilizing blaKPC.•Tn4401- and Tn7247-like structures differed in geographic distribution and plasmid/chromosome localization.•IS26 and IS6100 formed prevalent chimeric structures with truncated transposons to mobilize blaKPC.•Integrative mobilizable elements (IMEs) facilitated inter-cellular transfer of chromosomal blaKPC.

A significant proportion (∼11 %) of blaKPC genes were chromosome-integrated in P. aeruginosa.

Tn4401/Tn7247-like structures were the major transposons mobilizing blaKPC.

Tn4401- and Tn7247-like structures differed in geographic distribution and plasmid/chromosome localization.

IS26 and IS6100 formed prevalent chimeric structures with truncated transposons to mobilize blaKPC.

Integrative mobilizable elements (IMEs) facilitated inter-cellular transfer of chromosomal blaKPC.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) harboring blaKPC gene poses a formidable clinical challenge. However, the distribution and horizontal transfer mechanisms of blaKPC 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 blaKPC. In addition, 35,607 public P. aeruginosa genome sequences were acquired, among which 1,141 harbored blaKPC. Detailed analysis of the blaKPC genetic contexts in the combined dataset of the 1,220 P. aeruginosa genomes revealed that 10.4 % (174/1,680) of the blaKPC 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 blaKPC 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 blaKPC, 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 blaKPC genes, 13/174 were identified within integrative and mobilizable elements (IMEs). These findings offered new insights into the horizontal transmission mechanisms of blaKPC 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 blaKPC among clinical CRPA isolates.

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