Evidence map›Paper›PMID 41087874›Full record

ArticleBMC microbiology2025

Plasmid pHXY0908 confers ciprofloxacin heteroresistance to Salmonella enterica serovar typhimurium ATCC 14028 by regulating efflux pump gene expression.

Mengyuan Li, Xiaoyin Feng, Qianting Jian, Mou Jing, Xiran Wang, Zehua Cui, Rongmin Zhang, Jian Sun, Yahong Liu, Xiaoping Liao and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Mengyuan Li *National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Xiaoyin Feng *National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Qianting Jian *National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Mou JingNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Xiran WangNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Zehua CuiNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Rongmin ZhangNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Jian SunNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Yahong LiuNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China.
Xiaoping LiaoNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. xpliao@scau.edu.cn.
Xinlei LianNational Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, 510642, China. xinlei_lian@scau.edu.cn.

Funding

Guangdong Basic and Applied Basic Research Foundation 2020A1515010310Innovative Research Group Project of the National Natural Science Foundation of China 32121004International Cooperation and Exchange of the National Natural Science Foundation of China 31520103918National Key Research and Development Program of China 2023YFD1800101National Natural Science Foundation of China 32002336the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program 2019BT02N054
6 · The paper itself

Abstract

backgroundSalmonella enterica Serovar Typhimurium (S. Typhimurium) is a major global foodborne pathogen. In our previous study, the S. Typhimurium ATCC 14028 strain harboring plasmid pHXY0908 survived at fourfold its ciprofloxacin MIC (MIC0908 = 0.125 µg/mL), but the mechanism remained unclear. Heteroresistance, where minority subpopulations show elevated resistance, is among the key contributors to chronic, recurrent, and high-fatality infections. This study aimed to elucidate the molecular mechanisms by which plasmid pHXY0908 promotes ciprofloxacin heteroresistance in S. Typhimurium ATCC 14028.

resultsCiprofloxacin heteroresistance in ATCC 14,028-pHXY0908 was confirmed by population analysis profiling, antimicrobial susceptibility testing, and stability assessment. Whole-genome sequencing (WGS) and transcriptome (RNA-seq) analyses were performed to identify genomic variations and global transcriptional changes linked to the development of heteroresistance. WGS revealed minimal DNA mutations in subclones with increased MIC, with no single nucleotide variants detected in known ciprofloxacin resistance genes. Notably, plasmid pHXY0908 acquisition altered chromosomal interaction domains (CIDs), potentially affecting gene regulation. Weighted gene co-expression network analysis (WGCNA) of transcriptomic profiles identified a “brown” module comprising 168 eigengenes that were significantly correlated with MIC values. Within this module, the efflux pump genes acrA, acrB, and tolC exhibited high gene significance and module membership scores. Additional candidate genes potentially contributing to ciprofloxacin heteroresistance were identified, including sodB, yhiH, yfaV, STM14_2687, and pHXY0908-99. Notably, STM14_2687 (a LysR-type transcriptional regulator), negatively regulated acrAB-tolC; its overexpression suppressed acrA and enhancing susceptibility to ciprofloxacin. Furthermore, functional validation demonstrated that plasmid pHXY0908 could confer heteroresistance to ciprofloxacin in other Salmonella enterica strains, Escherichia coli, and Klebsiella pneumoniae, suggesting its broad-host-range potential in mediating heteroresistance.

conclusionOur study reveals that transcriptional regulation drives ciprofloxacin heteroresistance in S. Typhimurium ATCC 14028 carrying plasmid pHXY0908. We show that regulation of efflux pumps (e.g., acrAB-tolC), superoxide dismutase (sodB), DNA protection systems, and regulatory networks contributes to heteroresistance development. Plasmid pHXY0908 acquisition was found to confer ciprofloxacin heteroresistance across species, suggesting its potential for horizontal transfer and increased transmission risk. Notably, STM14_2687 was identified and validated as a transcription factor that represses acrAB-tolC expression and may serve as a potential therapeutic target.

Indexed as

Anti-Bacterial AgentsCiprofloxacinDrug Resistance, BacterialMembrane Transport ProteinsPlasmidsSalmonella typhimuriumBacterial ProteinsGene Expression Regulation, BacterialMicrobial Sensitivity TestsWhole Genome SequencingAnti-Bacterial AgentsBacterial ProteinsCiprofloxacinMembrane Transport ProteinsCiprofloxacinHeteroresistanceSalmonella enterica serovar typhimurium

Identifiers

PMID41087874
PMCPMC12523005

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Registered trials

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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.