A plasmid-encoded genetic switch orchestrates the bacterial virulence-fitness trade-off to drive antibiotic resistance dissemination
5 affiliations
- 1Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China
- 2Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, Chengdu, China
- 3School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, China
- 4Chengdu Academy of Educational Sciences, Chengdu, Sichuan, China
- 5Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, College of Life Sciences, Inner Mongolia University, Hohhot, China
Abstract
The global dissemination of multidrug-resistant plasmids poses a major threat to antimicrobial therapy. While these plasmids are known to carry antibiotic resistance genes, how they balance bacterial fitness and virulence to ensure their own persistence and dissemination remains unclear. Here, we identify a previously unannotated IncFII plasmid-encoded protein, which we name type 1 fimbrial repressor (T1FR). T1FR directly binds the fimS phase-variation switch, locking it in the “off” orientation to suppress type 1 fimbria (T1F) biogenesis, thereby attenuating bacterial adhesion, colonization, and pathogenicity. Concurrently, T1FR reprograms central carbon metabolism to offset the fitness cost of plasmid carriage, thereby enhancing plasmid transconjugative efficiency and host competitive fitness. This dual function is dynamically modulated by LtrA-mediated suppression of T1fr transcription, introducing plasticity into the virulence-fitness trade-off. Collectively, the LtrA-T1FR system orchestrates an evolutionary trade-off between plasmid fitness and host pathogenicity. Targeting the T1FR-T1F axis may offer a novel anti-adhesion therapeutic that avoids selection for antibiotic resistance.
IMPORTANCE: Bacterial resistance has become one of the most serious public health issues worldwide. The evolution and spread of drug-resistant plasmids represent one of the significant approaches for bacteria to acquire resistance, and drug-resistant bacteria often have a high mortality rate. However, the association and regulatory mechanism between antibiotic-resistant plasmids and bacterial virulence are currently unclear. The IncFII plasmid is considered an epidemic-resistant plasmid and plays a critical role in the widespread spread of carbapenem antibiotic resistance genes. This study identified a novel protein, T1FR type 1 fimbrial repressor), in IncFII plasmids and explored its regulatory mechanism by inhibiting the generation of host bacterial type 1 fimbriae, thereby weakening bacterial virulence and facilitating stable plasmid transmission. This study provides the scientific basis for understanding the correlation between bacterial resistance and virulence and promotes the scientific prevention and comprehensive management of bacterial infections.
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BibTeX
@article{wei2026plasmidencoded,
title = {{A plasmid-encoded genetic switch orchestrates the bacterial virulence-fitness trade-off to drive antibiotic resistance dissemination}},
author = {Hongcheng Wei and Wenlan Yang and Tiejun Zhang and Wei Xu and Ke Wu and Linghan Kong and Hao Li and Kailu Wang and Wenjun Yan and Ming Yang and Changyu Zhou and Songhua Li and Zhonghan Li and Changwei Lei and Hongning Wang},
journal = {mBio},
year = {2026},
month = sep,
doi = {10.1128/mbio.01899-26},
url = {https://doi.org/10.1128/mbio.01899-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A plasmid-encoded genetic switch orchestrates the bacterial virulence-fitness trade-off to drive antibiotic resistance dissemination
AU - Hongcheng Wei
AU - Wenlan Yang
AU - Tiejun Zhang
AU - Wei Xu
AU - Ke Wu
AU - Linghan Kong
AU - Hao Li
AU - Kailu Wang
AU - Wenjun Yan
AU - Ming Yang
AU - Changyu Zhou
AU - Songhua Li
AU - Zhonghan Li
AU - Changwei Lei
AU - Hongning Wang
PY - 2026
DA - 2026/09/16
JO - mBio
DO - 10.1128/mbio.01899-26
UR - https://doi.org/10.1128/mbio.01899-26
AB - The global dissemination of multidrug-resistant plasmids poses a major threat to antimicrobial therapy. While these plasmids are known to carry antibiotic resistance genes, how they balance bacterial fitness and virulence to ensure their own persistence and dissemination remains unclear. Here, we identify a previously unannotated IncFII plasmid-encoded protein, which we name type 1 fimbrial repressor (T1FR). T1FR directly binds the fimS phase-variation switch, locking it in the “off” orientation to suppress type 1 fimbria (T1F) biogenesis, thereby attenuating bacterial adhesion, colonization, and pathogenicity. Concurrently, T1FR reprograms central carbon metabolism to offset the fitness cost of plasmid carriage, thereby enhancing plasmid transconjugative efficiency and host competitive fitness. This dual function is dynamically modulated by LtrA-mediated suppression of T1fr transcription, introducing plasticity into the virulence-fitness trade-off. Collectively, the LtrA-T1FR system orchestrates an evolutionary trade-off between plasmid fitness and host pathogenicity. Targeting the T1FR-T1F axis may offer a novel anti-adhesion therapeutic that avoids selection for antibiotic resistance. IMPORTANCE: Bacterial resistance has become one of the most serious public health issues worldwide. The evolution and spread of drug-resistant plasmids represent one of the significant approaches for bacteria to acquire resistance, and drug-resistant bacteria often have a high mortality rate. However, the association and regulatory mechanism between antibiotic-resistant plasmids and bacterial virulence are currently unclear. The IncFII plasmid is considered an epidemic-resistant plasmid and plays a critical role in the widespread spread of carbapenem antibiotic resistance genes. This study identified a novel protein, T1FR type 1 fimbrial repressor), in IncFII plasmids and explored its regulatory mechanism by inhibiting the generation of host bacterial type 1 fimbriae, thereby weakening bacterial virulence and facilitating stable plasmid transmission. This study provides the scientific basis for understanding the correlation between bacterial resistance and virulence and promotes the scientific prevention and comprehensive management of bacterial infections.
SN - 2150-7511
ER -