Theriseofantimicrobialresistancelimitstherapeutic optionsforinfectionsbymethicillin-resistantstaphylococci. The staphylococcal cassette chromosome mec (SCC mec ) is a mobile genetic element as the only carrier of the methicillin-resistance determinants,the mecA or mecC gene.Theuseofantibiotics increases the spread of antibiotic resistance, but the mechanism by which antibiotics promote horizontal dissemination ofSCC mec islargely unknown. Inthis study, we demonstrate that many antibiotics, including -lactams, can induce the expression of ccrC1 and SCC mec excision from the bacterial chromosome. In particular, three widely used antibiotics targetingDNAreplicationandrepair(sulfamethoxazole, ciprofloxacin and trimethoprim) induced higher levels of ccrC1 expression and higher rates of SCC mec excision even at low concentrations (1/8×minimum inhibitory concentration). LexA was identified as a repressor of ccrC1 and ccrAB by binding to the promoter regions of ccrC1 and ccrAB . The activation of RecA after antibiotic induction alleviated the repression by LexA and increased the expression of ccrC1 or ccrAB , consequently increasing the excision frequency of the SCC mec for SCC mec transfer. These findings lead us to propose a mechanism by which antimicrobial agents can promote horizontal gene transfer of the mecA gene and facilitate the spread of methicillin resistance.