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Molecular epidemiology of levofloxacin-resistant Klebsiella pneumoniae and the association of plasmid-mediated quinolone resistance genes with key biological phenotypes.

Qian Zhang·Xinmiao Jia·Shiyu Chen·Peiyao Jia·Ying Zhu·Wei Yu·Xiaobing Chu·Zongping Li·Qiwen Yang
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Abstract

UNLABELLED: Klebsiella pneumoniae is a major opportunistic pathogen in China, yet the molecular epidemiology of quinolone resistance remains poorly characterized. This study analyzed 2,433 clinical isolates from 37 Chinese hospitals (2018-2022). The overall levofloxacin-non-susceptible (NS) rate was 53.60%, with urinary tract isolates showing higher resistance. Whole-genome sequencing identified 12 plasmid-mediated quinolone resistance (PMQR) genes. Among 1,304 NS strains, 74.54% carried at least one PMQR gene (mainly qnrS, qnrB, and aac(6')-Ib-cr), and 60.20% also had quinolone resistance-determining region (QRDR) mutations. Functional studies revealed diverse phenotypic impacts. Most PMQR genes conferred low-level resistance (minimum inhibitory concentration [MIC] = 1 mg/L), while qnrB52 and qnrB91 caused high-level resistance (MIC = 8-16 mg/L). Notably, qnrB91 reduced biofilm formation, indicating a trade-off between resistance and colonization. Growth assays showed that qnrB52, qnrB91, and qnrS1 inhibited normal growth, whereas qepA1 and qnrS1 enhanced growth under ethanol stress. Most PMQR genes (except qnrB6) attenuated bacterial adhesion. qepA1 promoted intracellular survival in macrophages, suggesting a role in chronic infection. Animal models confirmed that qnrB6, qnrB7, qnrVC6, and aac(6')-Ib-cr significantly enhanced virulence. This study is the first in China to report qnrVC6 and novel gyrA mutations (Ser83Ala/Val, Asp87Phe/His) in K. pneumoniae. It systematically reveals how PMQR genes influence infection by modulating resistance, immune evasion, and pathogenicity. These findings highlight that PMQR genes contribute not only to antibiotic resistance but also to virulence, suggesting that treatment strategies should consider specific PMQR genotypes. This research provides the largest-scale molecular epidemiological data and a theoretical basis for controlling quinolone-resistant K. pneumoniae in China. IMPORTANCE: Quinolone-resistant Klebsiella pneumoniae poses a serious threat to public health, yet the role of plasmid-mediated quinolone resistance (PMQR) genes beyond antibiotic resistance remains underexplored. In this largest-scale multicenter study in China, we analyzed 2,433 clinical isolates and discovered that PMQR genes do more than just confer drug resistance-they also influence bacterial growth, stress survival, biofilm formation, and the ability to evade or persist within host immune cells. Some PMQR genes even enhance virulence in an animal model. These findings challenge the traditional view of resistance genes as mere contributors to drug failure, revealing that they can also shape infection outcomes by altering bacterial behavior. Understanding these dual roles may guide more precise treatment strategies targeting specific PMQR genotypes.

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Klebsiella pneumoniaeKlebsiella InfectionsPlasmidsAnimalsLevofloxacinAnti-Bacterial AgentsQuinolonesHumansChinaMicrobial Sensitivity TestsMolecular EpidemiologyMiceBacterial ProteinsDrug Resistance, BacterialPhenotypeWhole Genome SequencingVirulenceDrug Resistance, Multiple, BacterialPMQRQRDRepidemiologyquinolone resistanceJournal Article

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Qian Zhang, Xinmiao Jia, Shiyu Chen, Peiyao Jia, Ying Zhu, Wei Yu, Xiaobing Chu, Zongping Li, Qiwen Yang. 2026-05-20. Molecular epidemiology of levofloxacin-resistant Klebsiella pneumoniae and the association of plasmid-mediated quinolone resistance genes with key biological phenotypes.. https://doi.org/10.1128/spectrum.01031-26

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