Emerging and re-emerging KPC-producing hypervirulent Pseudomonas aeruginosa ST697 and ST463 between 2010 and 2021

ABSTRACT

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been a major threat to human health due to its increased morbidity and mortality in clinical settings. Carbapenemase genes are less frequently found in CRPA compared with carbapenem-resistant Enterobacterales, of which carbapenemase producers are common. In this study, we identified 11 bla_KPC-2-harbouring P. aeruginosa isolates from 139 carbapenemase-insensitive P. aeruginosa isolates collected between 2010 and 2021 in a tertiary hospital in China. Nine isolates belonged to ST697, while the other two were ST463. The antibiotic susceptibility testing showed that all the isolates were multidrug resistant, including resistance to imipenem, meropenem, ceftazidime, and tigecycline. Patients with Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing P. aeruginosa infections were mostly associated with complicated diseases and prolonged hospital stay, with 30% deterioration. The whole-genome sequencing analysis showed that these isolates carried multiple antibiotic resistance genes and virulence genes, and the KPC-2 genetic elements were highly related in ST697 isolates. The complete sequencing of ST697 isolate SE5416 showed that the harbouring of bla_KPC-2 resulted from complex transposition and homologous recombination of an Inc_pRBL16 plasmid and other mobile elements. The Galleria mellonella infection model experiment showed that these KPC-2-producing P. aeruginosa–infected larvae had low survival rates and high virulence. The present study revealed the shifting of CRPA from ST697 to ST463 in East China; ST463 had higher drug resistance, posing greater challenges for clinical management.

KEYWORDS:

• Carbapenems
• KPC-2
• Pseudomonas aeruginosa (P. aeruginosa)
• resistance
• virulence

Acknowledgments

We are grateful for professor Dongsheng Zhou from State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology for the assistance in the drawing of figures.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the Science Foundation of Jiangsu Province Health Department [grant number ZDB2020014], the Science Foundation of Suzhou Health Department [grant number LCZX202106], and the Discipline Construction Program of the Second Affiliated Hospital of Soochow University [grant number XKTJ-TD202001].