Antimicrobial resistance (AMR) is a global challenge in both clinical and food safety. The increasing prevalence of resistant strains is challenging treatment and control measures against microbial pathogens. Metal ions are common in environmental and food systems, and can affect bacterial physiology, resistance mechanisms, and antibiotic activity. This study examines the influence of four metal ions (Fe²⁺, Mg²⁺, Mn²⁺ and NH₄⁺) on the antibacterial effectiveness of four groups of antibiotics (amoxicillin, ampicillin, erythromycin and ciprofloxacin) against a series of clinically relevant pathogens (Escherichia coli, Staphylococcus aureus Pseudomonas aeruginosa and Serratia marcescens), in addition to foodborne organisms. We show that metal ions potentiate antibiotic activity in a species- and concentration-dependent manner, affecting both resistance and survival of the bacteria. Moreover, Fe²⁺ dramatically decreased both sensitivity to erythromycin and ciprofloxacin in E. coli and abolished antibiotic function completely in S. aureus at high concentrations, which may involve a more rigid cell envelope preventing drug penetration. In P. aeruginosa, Mn²⁺ also caused step-by-step resistance to ciprofloxacin and then enhanced oxidative stress protection and efflux pump were likely involved therein. In contrast, the effect of NH₄⁺ on S. marcescens was little and ciprofloxacin showed similar bactericidal activity at different concentrations. These findings point to a complex interplay of environmental metal exposure and antibiotic resistance within clinical and food-associated pathogens, suggesting that the levels of metal ions should be considered when targeting AMR in both food processing and clinical environments.
