Iron and zinc ions, potent weapons against multidrug-resistant bacteria

Drug-resistant bacteria are becoming an increasingly widespread problem in the clinical setting. The current pipeline of antibiotics cannot provide satisfactory options for clinicians, which brought increasing attention to the development and application of non-traditional antimicrobial substances as alternatives. Metal ions, such as iron and zinc ions, have been widely applied to inhibit pathogens through different mechanisms, including synergistic action with different metabolic enzymes, regulation of efflux pumps, and inhibition of biofilm formation. Compared with traditional metal oxide nanoparticles, iron oxide nanoparticles (IONPs) and zinc oxide nanoparticles (ZnO-NPs) display stronger bactericidal effect because of their smaller ion particle sizes and higher surface energies. The combined utilization of metal NPs (nanoparticles) and antibiotics paves a new way to enhance antimicrobial efficacy and reduce the incidence of drug resistance. In this review, we summarize the physiological roles and bactericidal mechanisms of iron and zinc ions, present the recent progress in the research on the joint use of metal NPs with different antibiotics, and highlight the promising prospects of metal NPs as antimicrobial agents for tackling multidrug-resistant bacteria.