Antihistamine drug loratadine at environmentally relevant concentrations promotes conjugative transfer of antibiotic resistance genes: Coeffect of oxidative stress and ion transport.

Due to the widespread use of loratadine (LOR) as an antihistamine, it is widely distributed in the environment as an emerging contaminant. However, its impact on the dissemination of antibiotic resistance genes (ARGs) remains unclear. This study investigated the effect of LOR on the conjugative transfer of ARGs and elucidated the potential mechanisms through transcriptome analysis. The results showed that LOR significantly promoted the frequency of conjugative transfer up to 1.5- to 8.6-fold higher compared with the control group. Exposure to LOR increased reactive oxidative species (ROS) and intracellular Ca ²⁺ concentrations, leading to the upregulation of expression of genes related to transmembrane transport and SOS response. Meanwhile, it stimulated the increase of cell membrane permeability. Moreover, LOR exposure could enhance H ⁺ efflux in donor bacteria, resulting in the decrease of intracellular pH and the elevation of transmembrane potential, which could induce the increase of ion transport, thereby promoting plasmid efflux from the cell membrane. Based on this, we inferred that LOR can induce an increase in ROS level and intracellular Ca ²⁺ concentrations, and promoted the efflux of intracellular H ⁺ . This, in turn, triggered the intensification of various ion transport processes on the cell membrane, thereby increasing membrane permeability and accelerating plasmid efflux. Ultimately, the coeffect of oxidative stress response and ion transport promoted conjugative transfer. This study demonstrated that LOR significantly promotes plasmid-mediated conjugative transfer of ARGs, providing novel insights into the mechanisms underlying this process.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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