RationaleThe rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antimicrobials. Apart from horizontal gene transfer and plasmid mediated antimicrobial resistance (AMR) acquisition, co-exposure of heavy metals and antibiotics cause to emerge AMR Enterobacteriaceae. Heavy metals and antimicrobials co-exist in many environmental settings. We hypothesized that heavy metals and lower dose of antibiotic co-exposure may alter levels of antimicrobial susceptibility and facilitate to emerge AMR bacteria.MethodsThe growth kinetics of antimicrobial susceptible Staphylococcus aureus ST80 was carried out in the presence of chromium/cadmium salt and a lower dose of antibiotics. Subsequently, the antimicrobials susceptibility patterns of heavy metals pre-exposed for 48 hours Staphylococcus aureus ST 80 was determined by Kirby-Bauer disc diffusion method.ResultsThe antimicrobial susceptibility profile revealed that the zone of inhibition (ZOI) for ampicillin, amoxicillin, ciprofloxacin and doxycycline significantly decreased in chromium pre-exposed Staphylococcus compared to unexposed bacteria. However, cadmium pre-exposed bacteria only showed significant decreased ZOI for amoxicillin. Moreover, the MIC of amoxicillin was increased by 8-fold in chromium and 32-fold in cadmium with a low-dose of amoxicillin co-exposed bacteria. Besides, the RT-qPCR data demonstrated that chromium and a low-dose of amoxicillin pre-exposed significantly increased the mRNA expression of femX (25-fold), mepA (19-fold) and norA (17-fold) in S. aureus.In essence, minimum levels of chromium/cadmium and a MIC of amoxicillin exposure induced efflux pumps, which might responsible to emerge amoxicillin resistant S. aureus.