Regulatory Mechanisms of Zinc on Bacterial Antibiotic Resistance and Virulence in a One Health Context

Zinc (Zn), a ubiquitous environmental transition metal primarily existing as Zinc ions (Zn2+), plays a critical role in various biological processes. Its extensive application in agriculture, industry, and healthcare has led to significant environmental contamination. However, the mechanistic contribution of Zn2+ to bacterial antibiotic resistance and virulence remains insufficiently understood. This review explores the sources, cycling, and environmental accumulation of Zn2+ in a One Health context, emphasizing their impact on bacterial antibiotic resistance and virulence. Zn2+ promote bacterial antibiotic resistance by regulating efflux pumps, biofilm formation, expression and transfer of antibiotic resistance genes, as well as synergistic effects with other heavy metals and antibiotics. Meanwhile, Zn2+ promote bacterial virulence by regulating quorum sensing, secretion and metal homeostasis systems, as well as oxidative stress response and virulence factor expression. Additionally, it highlights the potential of targeting Zn homeostasis as a strategy to combat environmental antibiotic resistance. Collectively, these findings provide key insights into the mechanisms by which Zn2+ regulate bacterial antibiotic resistance and pathogenicity, offering valuable guidance for developing strategies to mitigate the global threat of antibiotic resistance.