Antibiotics and common antibacterial biocides stimulate horizontal transfer of resistance at low concentrations

There is a rising concern that antibiotics, and possibly other antimicrobial agents, can promote horizontal transfer of antibiotic resistance genes. For most types of antimicrobials their ability to induce conjugation below minimal inhibitory concentrations (MICs) is still unknown. Our aim was therefore to explore the potential of commonly used antibiotics and antibacterial biocides to induce horizontal transfer of antibiotic resistance. Effects of a wide range of sub-MIC concentrations of the antibiotics cefotaxime, ciprofloxacin, gentamicin, erythromycin, sulfamethoxazole, trimethoprim and the antibacterial biocides chlorhexidine digluconate, hexadecyltrimethylammoniumchloride and triclosan were investigated using a previously optimized culture-based assay with a complex bacterial community as a donor of mobile resistance elements and a traceable Escherichia coli strain as a recipient. Chlorhexidine (24.4μg/L), triclosan (0.1mg/L), gentamicin (0.1mg/L) and sulfamethoxazole (1mg/L) significantly increased the frequencies of transfer of antibiotic resistance whereas similar effects were not observed for any other tested antimicrobial compounds. This corresponds to 200 times below the MIC of the recipient for chlorhexidine, 1/20 of the MIC for triclosan, 1/16 of the MIC for sulfamethoxazole and right below the MIC for gentamicin. To our best knowledge, this is the first study showing that triclosan and chlorhexidine could stimulate the horizontal transfer of antibiotic resistance. Together with recent research showing that tetracycline is a potent inducer of conjugation, our results indicate that several antimicrobials including both common antibiotics and antibacterial biocides at low concentrations could contribute to antibiotic resistance development by facilitating the spread of antibiotic resistance between bacteria.