Quorum-Sensing C12-HSL Drives Antibiotic Resistance Plasmid Transfer via Membrane Remodeling, Oxidative Stress, and RpoS-RMF Crosstalk

Yang, Yang; Wu, Ziyan; Zhu, Li’e; Han, Zixin; Li, Junpeng; Fang, Qiaoqiao; Zhu, Guoqiang

doi:10.3390/microorganisms13081837

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Quorum-Sensing C12-HSL Drives Antibiotic Resistance Plasmid Transfer via Membrane Remodeling, Oxidative Stress, and RpoS-RMF Crosstalk

by

Yang Yang

^1,2,*,†

,

Ziyan Wu

^1,2,†,

Li’e Zhu

^1,2

,

Zixin Han

^1,2,

Junpeng Li

^1,2,

Qiaoqiao Fang

^1,2 and

Guoqiang Zhu

^1,2,*

¹

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China

²

Jiangsu Co-Innovation Center for Important Animal Infectious Diseases and Zoonoses, Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu, Yangzhou 225009, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Microorganisms 2025, 13(8), 1837; https://doi.org/10.3390/microorganisms13081837

Submission received: 5 July 2025 / Revised: 31 July 2025 / Accepted: 5 August 2025 / Published: 6 August 2025

(This article belongs to the Section Antimicrobial Agents and Resistance)

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Abstract

Antibiotic misuse accelerates resistance dissemination via plasmid conjugation, but quorum sensing (QS) regulatory mechanisms remain undefined. Using Escherichia coli (E. coli) MG1655 conjugation models (RP4-7/EC600 plasmids), we demonstrate that long-chain acyl-homoserine lactones (C10/C12-HSL) enhance transfer frequency by up to 7.7-fold (200μM C12-HSL; p < 0.001), while quorum-quenching by sub-inhibitory vanillin suppressed this effect by 95% (p < 0.0001). C12-HSL compromised membrane integrity via ompF upregulation (4-fold; p < 0.01) and conjugative pore assembly (trbBp upregulated by 1.38-fold; p < 0.05), coinciding with ROS accumulation (1.5-fold; p < 0.0001) and SOS response activation (recA upregulated by 1.68-fold; p < 0.001). Crucially, rpoS and rmf deletion mutants reduced conjugation by 65.5% and 55.8%, respectively (p < 0.001), exhibiting attenuated membrane permeability (≤65.5% reduced NPN influx; p < 0.0001), suppressed ROS (≤54% downregulated; p < 0.0001), and abolished transcriptional induction of conjugation/stress genes. Reciprocal RpoS–RMF (ribosomal hibernation factor) crosstalk was essential for AHL responsiveness, with deletions mutually suppressing expression (≤65.9% downregulated; p < 0.05). We establish a hierarchical mechanism wherein long-chain AHLs drive resistance dissemination through integrated membrane restructuring, stress adaptation, and RpoS–RMF-mediated genetic plasticity, positioning QS signaling as a viable target for curbing resistance spread.

Keywords: quorum sensing; ribosomal hibernation factor; plasmid conjugation

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MDPI and ACS Style

Yang, Y.; Wu, Z.; Zhu, L.; Han, Z.; Li, J.; Fang, Q.; Zhu, G. Quorum-Sensing C12-HSL Drives Antibiotic Resistance Plasmid Transfer via Membrane Remodeling, Oxidative Stress, and RpoS-RMF Crosstalk. Microorganisms 2025, 13, 1837. https://doi.org/10.3390/microorganisms13081837

AMA Style

Yang Y, Wu Z, Zhu L, Han Z, Li J, Fang Q, Zhu G. Quorum-Sensing C12-HSL Drives Antibiotic Resistance Plasmid Transfer via Membrane Remodeling, Oxidative Stress, and RpoS-RMF Crosstalk. Microorganisms. 2025; 13(8):1837. https://doi.org/10.3390/microorganisms13081837

Chicago/Turabian Style

Yang, Yang, Ziyan Wu, Li’e Zhu, Zixin Han, Junpeng Li, Qiaoqiao Fang, and Guoqiang Zhu. 2025. "Quorum-Sensing C12-HSL Drives Antibiotic Resistance Plasmid Transfer via Membrane Remodeling, Oxidative Stress, and RpoS-RMF Crosstalk" Microorganisms 13, no. 8: 1837. https://doi.org/10.3390/microorganisms13081837

APA Style

Yang, Y., Wu, Z., Zhu, L., Han, Z., Li, J., Fang, Q., & Zhu, G. (2025). Quorum-Sensing C12-HSL Drives Antibiotic Resistance Plasmid Transfer via Membrane Remodeling, Oxidative Stress, and RpoS-RMF Crosstalk. Microorganisms, 13(8), 1837. https://doi.org/10.3390/microorganisms13081837

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Quorum-Sensing C12-HSL Drives Antibiotic Resistance Plasmid Transfer via Membrane Remodeling, Oxidative Stress, and RpoS-RMF Crosstalk

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