Characteristics of rare ST463 carbapenem-resistant Pseudomonas aeruginosa clinical isolates from blood

Objectives: This study aimed to elucidate resistance to carbapenems and fluoroquinolones, the transmis-sion mechanism of blaKPC-2, and the virulence characteristics of a Pseudomonas aeruginosa strain (TL3773) isolated in East China.Methods: The virulence and resistance mechanisms of TL3773 were investigated by whole genome se-quencing (WGS), comparative genomic analysis, conjugation experiments, and virulence assays. Results: This study isolated carbapenem-resistant P. aeruginosa from blood resistant to carbapen-ems. The patient's clinical data showed poor prognosis compounded by multiple sites of infec-tion. WGS showed that TL3773 carried aph (3')-IIb, blaPAO, bla OXA-486, fosA, catB7, and two crpP re-sistance genes on chromosome, and the carbapenem resistance gene blaKPC-2 on plasmid. We iden-tified a novel crpP gene named TL3773-crpP2. Cloning experiments proved that TL3773-crpP2 was not the primary cause of fluoroquinolone resistance in TL3773. GyrA and ParC mutations may con-fer fluoroquinolone resistance. The blaKPC-2 genetic environment was IS26-TnpR-ISKpn27- blaKPC-2-ISKpn6- IS26-Tn3-IS26, potentially mediating the transmission of blaKPC-2 in P. aeruginosa. The overall vir-ulence of TL3773 was lower than that of PAO1. However, the pyocyanin and biofilm formation of TL3773 was higher than that of PAO1. WGS further indicated that TL3773 was less virulent than PAO1. Phylogenetic analysis showed that TL3773 was most similar to the P. aeruginosa isolate ZYPA29 from Hangzhou, China. These observations further indicate that ST463 P. aeruginosa is rapidly spreading.Conclusions: The threat of ST463 P. aeruginosa harbouring blaKPC-2 is emergent and may pose a threat to human health. More extensive surveillance and effective actions are urgently needed to control its further spread.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )