Plasmid binding to metal oxide nanoparticles inhibited lateral transfer of antibiotic resistance genes

Abstract

Lateral gene transfer (LGT) promotes the proliferation of antibiotic resistance genes (ARGs). However, the lateral transfer efficiency of ARGs in the natural environment is little known. This study explored the lateral transfer of ARG-carrying plasmids to Escherichia coli (i.e., transformation) in the presence of metal oxide nanoparticles (MONPs). The presence of ZnO, Al₂O₃ and TiO₂ nanoparticles (ZnONPs, Al₂O₃NPs and TiO₂NPs, respectively) at concentrations of less than 50 mg L⁻¹ inhibited the lateral transfer of pUC19 plasmid carrying the ampicillin resistance gene into E. coli DH5α in a decreasing degree of Al₂O₃NP > ZnONP > TiO₂NP. The suppressed lateral ARG transfer was not due to the dissolution of metal ions from MONPs, but rather was caused by the binding of MONPs with the phosphate groups and bases of pUC19, as supported by microscopic, spectroscopic and computational evidence. The amount of plasmids bound to MONPs showed a significant negative correlation with the efficiency of ARG transfer, likely because plasmids and MONPs formed aggregates that were blocked out of E. coli cells, thus inhibiting the ARG lateral transfer. Our results provided new insight into the effect of MONPs on the lateral transfer of ARGs and improved our understanding of the ecological risks of plasmid-borne ARGs at the molecular and cellular level.