Bisphenols promote the conjugative transfer of antibiotic resistance genes without damaging cell membrane

The global dissemination of antibiotic resistance is severely threatening public health. Several non-antibiotic chemicals facilitate the horizontal transfer of antibiotic resistance genes. Bisphenol analogs, e.g., bisphenol S and bisphenol AF, are known pollutants, yet their effects on the propagation and spread of antibiotic resistance genes remain unknown. Our study demonstrates for the first time that bisphenol S and bisphenol AF at environmentally relevant concentrations of 0.1–100.0 μg/L accelerates 2–5 folds the conjugative transfer frequency of RP4 plasmid-borne antibiotic resistance genes within and across bacterial genera, from Escherichia coli DH5α to Escherichia coli HB101 or Salmonella enterica. Bisphenol S and bisphenol AF exerted no effect on the bacterial growth and little change in cell membrane permeability. Accelerated conjugative transfer is explained by the repression of the global regulator, with a maximum relative expression level of 0.23, and of the vertical transfer system (0.26), with simultaneous up-regulation of DNA horizontal transfer and replication system (3.66). This bisphenols-induced conjugative transfer of antibiotic resistance genes could promote the spread of antibiotic resistance in the environment and in gut microbial communities of wildlife and human.