ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1623241
This article is part of the Research TopicTransmission dynamics and population genomics of superbug pathogens of public health importanceView all 7 articles
Tracing the evolutionary trajectory of the IncP-2 plasmid co-harboring blaIMP-45 and blaVIM-1 : an outbreak of Pseudomonas aeruginosa co-producing IMP-45 and VIM-1 carbapenemases in China
Provisionally accepted
- 1Peking University China-Japan Friendship School of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China
- 2China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China
- 3Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China
- 4Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- 5Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China., Beijing, China
- 6Yanjing Medical College, Capital Medical University, Beijing, China
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Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant global health risk, particularly for immunocompromised individuals. This study documents an outbreak of CRPA strains co-harboring blaVIM-1 and blaIMP-45 on IncP-2 plasmids in a Chinese tertiary hospital, resulting in poor outcomes for transplant patients.Methods: 17 ST313 VIM-1-IMP-45 CRPA strains were collected from transplant patients, and antibiotic susceptibility was tested via microbroth dilution. Whole genome sequencing (WGS) identified drug resistance and virulence mechanisms, analyzed ST313 P. aeruginosa phylogeny, and traced blaVIM-1 and blaIMP-45 origins. Conjugation experiments were conducted to assess the conjugative potential of the IncP-2 plasmid co-harboring blaVIM-1 and blaIMP-45. Structural and molecular docking studies explored the PBP3 (P527S) mutation's role in aztreonam resistance.Results: From February 2022 to July 2024, 17 ST313 VIM-1-IMP-45 CRPA strains from 10 transplant patients were identified. All strains were extensively drug-resistant but sensitive to colistin and cefiderocol. WGS showed blaIMP-45 and blaVIM-1 on an IncP-2 megaplasmid. Phylogenetic analysis indicated high homology with plasmids carrying blaIMP-45. Further analysis of the genetic environment showed that the IncP-2 plasmid co-harboring blaVIM-1 and blaIMP-45 was formed by the insertion of a Tn3-family transposon carrying blaVIM-1 into the IncP-2 plasmid carrying blaIMP-45. In addition aztreonam-resistant strains (14/15) had a PBP3 (P527S) mutation, with molecular docking studies suggesting reduced aztreonam binding.Conclusions: This study reports a clonal outbreak of ST313 P. aeruginosa strains co-producing IMP-45 and VIM-1 carbapenemases in a tertiary hospital. The evolutionary path of the IncP-2 plasmid co-harboring blaIMP-45 and blaVIM-1 was elucidated.
Keywords: Carbapenem-resistant Pseudomonas aeruginosa, CRPA, horizontal gene transfer (HGT), Nosocomial infection, Metallo-beta-lactamase (MBL), Resistance dissemination
Received: 05 May 2025; Accepted: 02 Jun 2025.
Copyright: © 2025 Ma, Lei, Zhang, Liu, Zhang, Zu, Yang, Li and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Binghuai Lu, Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China
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