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Monoterpenoid phenols efficiently inhibit the conjugative transfer of bla NDM -positive IncX3 plasmid within and across bacterial genera
Journal article   Open access

Monoterpenoid phenols efficiently inhibit the conjugative transfer of bla NDM -positive IncX3 plasmid within and across bacterial genera

Junjie Wang, Feng-Jing Song, Caihong Guo, Jully Gogoi Tiwari, Henry Annandale, Zhi-Yuan You, Liuxi Liyi, Chao Jie, Ming Zou and Bao-Tao Liu
Journal of Hazardous Materials Advances, Vol.22, 101251
2026
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Open Access CC BY-NC-ND V4.0

Abstract

Monoterpenoid phenols (MPs) Conjugative transfer IncX3 plasmid bla NDM Gene expressions
The spread of antibiotic resistance genes, especially bla NDM , poses a huge threat to public health and inhibiting their transfer is imperative. In this study, we explored the effect of plant-derived monoterpenoid phenols (MPs) including carvacrol and thymol, on the efficiency of intra-and inter-genus transfer of IncX3 plasmid with bla NDM at different temperatures. Escherichia coli carrying bla NDM-positive IncX3 plasmid was used as the donor, and rmtB-positive E. coli or bla KPC-2-positive Klebsiella pneumoniae were the intra-and inter-genera recipients, respectively. The bla NDM plasmid could transfer within and across genera, and maintained stability after multiple passages without antibiotic, highlighting that reducing the use of antibiotics might not be enough to reduce the risk of horizontal gene transfer (HGT). Exposure to sub-minimum inhibition concentrations (sub-MICs) of MPs significantly inhibited the conjugative transfer of IncX3 bla NDM plasmid within and across genera at 25 • C and 37 • C, respectively. The inhibitory effect of carvacrol on the plasmid conjugative transfer was further validated in an animal model. The MPs exposure reduced ATP levels and cell membrane permeability in donor and recipient bacteria, and the ATP reduction was concentration-dependent. Sub-MICs of MPs significantly decreased the expression levels of genes related to ATP synthesis, reactive oxygen species generation and SOS response in the donor. These effects collectively hinder conditions favorable to plasmid transfer. This study is the first to provide new insights into possible underlying mechanisms for using carvacrol and thymol to inhibit the conjugative transfer and dissemination of prevalent bla NDM-positive IncX3 plasmid in animal production. These findings provided new strategies for controlling antibiotic resistance.

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