ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
This article is part of the Research TopicGenomic and Transcriptomic Insights into ESKAPE Pathogens' Antimicrobial ResistanceView all 3 articles
Polymyxin-resistant hypervirulent Klebsiella pneumoniae clinical isolates from a tertiary hospital in China: Molecular Mechanisms, Antimicrobial Susceptibility, and Virulent Phenotypes
Provisionally accepted
- 1The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China
- 2The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- 3Zhejiang Hospital, Hangzhou, China
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Background: Polymyxins are critical last-resort treatments for infections caused by multidrug-resistant (MDR) gram-negative bacteria, especially carbapenem-resistant isolates. Recently, there has been a continuous increase in reports of polymyxin-resistant Klebsiella pneumoniae (PoRKP), which poses a major healthcare challenge. This study aims to investigate the current epidemiological trends and virulent phenotypes of PoRKP and to elucidate the mechanisms underlying polymyxin resistance. Methods: In this study, 17 PoRKP strains were retrospectively identified from 2,146 Klebsiella pneumoniae (KP) clinical isolates collected in Hangzhou city from 2018 to 2021. We assessed the antimicrobial resistance and virulence profiles of 17 isolates, and they were subjected to molecular and genetic analyses and antimicrobial susceptibility testing. Results: The overall polymyxin resistance rate among the bacterial isolates included in this study was low (0.8%); however, all PoRKP isolates were MDR-positive. Notably, only three isolates carried mcr, whereas the vast majority either harbored mutations in mgrB (C28R or C28Y) or pmrA (T246A and R256G) leading to overexpression of the two-component systems, which we consider to be the primary mechanism underlying polymyxin resistance. Furthermore, five PoRKP isolates carrying hypervirulence genes exhibited a virulent phenotype in a Galleria mellonella infection model. Finally, recent antibiotic therapy, invasive procedures, and age were identified as important risk factors for the occurrence of polymyxin-resistant strains. Conclusion: Our findings indicated a relatively low prevalence of plasmid-mediated mobile polymyxin resistance genes among PoRKP isolates, whereas the upregulation of the two-component systems (particularly phoPQ) played a more prominent role in mediating polymyxin resistance.
Keywords: Hypervirulent, mgrB, PhoPQ, polymyxin-resistant Klebsiella pneumoniae, Virulence
Received: 15 Sep 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Zhu, Yan, Lai, Zou, Chen, Tang, Wang and He. 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:
Xiaofang Tang
Qiang Wang
Yuzhou He
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