Mechanistic insight into curcumin-induced conjugative plasmid transfer acceleration: Role of intracellular arginine...

Curcumin exhibits a broad spectrum of applications spanning multiple domains, including its incorporation in dietary supplements, functional beverages, cosmetic formulations, and nutraceutical products. Nevertheless, its potential influence on the development of antibiotic resistance remains to be fully elucidated. Therefore, this study aims to investigate the effects of curcumin on the conjugative transfer of plasmids carrying antibiotic resistance genes (ARGs). Our findings indicate that curcumin significantly enhanced the transfer of RP4 plasmid, as well as clinically relevant plasmids carrying bla_NDM, mcr-1 and tet(X4). Further mechanisms analysis revealed that curcumin facilitated plasmid conjugation transfer by increasing bacterial membrane permeability, inducing oxidative stress, and accelerating energy metabolism, while altering the expression levels of key genes involved in horizontal gene transfer (HGT). Notably, curcumin elevated intracellular arginine levels, and exogenous arginine supplementation further promoted plasmid transfer. Arginine uptake genes (artJ, artI and argT) were upregulated following curcumin exposure, and the absence of artJ significantly attenuated curcumin-induced arginine accumulation and plasmid transfer, demonstrating the crucial role of the artJ gene in facilitating curcumin-induced plasmid transfer through its promotion of arginine uptake. These findings provide new insights into an unrecognized risk of curcumin in potentially accelerating the spread of antibiotic resistance, highlight the unintended consequences of curcumin use in the food industry.