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An environment co-contaminated with metals and antibiotics ultimately exposes bacteria to these metals and antibiotics simultaneously. This study aims to explore the efficacy of sublethal concentrations of copper ions contaminated with tetracycline regarding antibiotic resistance in a sensitive strain of E. coli K12. The study proved that a copper ions and tetracycline co-contaminated environment could considerably enhance the mutation frequencies of chloramphenicol and polymyxin B resistance in antibiotic susceptible E. coli; however, the equivalent copper ions and tetracycline alone showed weaker effects. Results also demonstrated that an environment co-contaminated with relatively high sublethal concentrations of copper ion and tetracycline co-contaminated environment could induce much higher antibiotic resistance than the low sublethal and control groups. Whole-genome characterization results indicated that variability existed within the genotype and phenotype involved in antibiotic resistance. Additionally, the evolved resistant strains displayed hereditary resistance after 5 round culture cycles in LB broth over 5 days. Results implied that co-contamination with metals and antibiotics environment could strengthen resistance and contribute to the induction and dissemination of antibiotic resistance in metal and antibiotic co-contaminated environment. [ABSTRACT FROM AUTHOR]