Evidence map›Paper›PMID 41975405›Full record

ArticleAnnals of clinical microbiology and antimicrobials2026

Within-host mechanisms of resistance evolution in polymyxin B-resistant Klebsiella pneumoniae without prior exposure.

Jun Li, Yuyao Wang, Haolan Wang, Zhaojun Liu, Yubing Xia, Yongmei Hu, Haichen Wang, Fengjun Xia, Mingxiang Zou

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Article in Annals of clinical microbiology and antimicrobials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jun LiDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yuyao WangDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Haolan WangDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Zhaojun LiuDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yubing XiaDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yongmei HuDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Haichen WangDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Fengjun XiaDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Mingxiang ZouDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. zoumingxiang@csu.edu.cn.

Funding

college students' innovations special project funded by Central South University S202510533482college students' innovations special project funded by Central South University S202510533511Merck Sharp & Dohme 100759
6 · The paper itself

Abstract

backgroundPolymyxin B-resistant Klebsiella pneumoniae (PBR-KP) has been emerging as a significant concern. This study investigated the within-host mechanisms of resistance evolution in PBR-KP without prior PB exposure.

methodsSix groups were enrolled [PB-sensitive K. pneumoniae (PBS-KP) evolved into PBR-KP from the same patient], and antimicrobial susceptibility testing was conducted using the microdilution broth method. Whole-genome sequencing was performed to analyze molecular characteristics, and to investigate the resistance mechanisms, gene expression analysis of pmrAB, phoPQ, crrAB, and eptA was performed using RT-qPCR. Fitness costs were assessed through biofilm formation, in vitro growth rate, and virulence analysis.

resultsAll 12 strains belonged to ST11-KL64, except for PB9 and PB10, which were classified as ST11-KL47. Each resistant strain was highly related to its corresponding sensitive strain. The relative expression levels of phoPQ, eptA, and pmrAB were significantly upregulated in most PBR-KP strains. PBR-KP strains exhibited no fitness cost regarding in vitro growth rate and biofilm formation. Notably, the eptA gene was highly expressed in the four PBR-KP strains with enhanced virulence, indicating its association with virulence. Furthermore, PBR-KP strains with enhanced virulence were highly associated with KL64, whereas those without enhanced virulence were linked to KL47, except for PB12, indicating a potential relationship between virulence and serotype.

conclusionsPB resistance can develop in KP strains without prior exposure to the drug, possibly driven by upregulation of phoPQ, pmrAB, and eptA, as supported by validated transcriptomics data. These resistant strains did not exhibit fitness costs related to biofilm formation or growth rate. Enhanced virulence, found in most PBR-KP strains, may be closely associated with eptA overexpression and specific serotypes.

Indexed as

Anti-Bacterial AgentsDrug Resistance, BacterialKlebsiella pneumoniaePolymyxin BBacterial ProteinsBiofilmsGene Expression Regulation, BacterialHumansKlebsiella InfectionsMicrobial Sensitivity TestsVirulenceWhole Genome SequencingAnti-Bacterial AgentsBacterial ProteinsPolymyxin BFitness costKlebsiella pneumoniaPolymyxin B resistantResistance mechanismVirulence

Identifiers

PMID41975405
PMCPMC13262486

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.