Stereoselective Behavior of Naproxen Chiral Enantiomers in Promoting Horizontal Transfer of Antibiotic Resistance Genes

Abstract

Antibiotic resistance poses a global threat to public health, with recent studies highlighting the role of non-antibiotic pharmaceuticals in the transmission of Antibiotic resistance genes (ARGs). This study provides insights into the comprehensive profile, horizontal gene transfer potential, hosts, and public health risks associated with antibiotic resistomes in river ecosystems exposed to chiral naproxen (NAP). Our findings demonstrate that NAP stress selectively enriches ARGs and mobile genetic elements (MGEs), thereby bolstering bacterial resistance to specific antibiotics. Importantly, the spatial variation of NAP chiral enantiomers influences the enantioselective response of bacterial communities to antibiotics. While (S)-NAP and (R)-NAP exhibit differing degrees of horizontal transfer potential, (S/R)-NAP notably facilitates microbial aggregation and DNA transport via type IV secretion system (T4SS)-related functional genes, promoting the conjugation of sul1. Moreover, (S/R)-NAP promotes the horizontal transfer of ARGs by stimulating ROS production and altering cell membrane permeability. Chiral NAP exposure induces pathogens to acquire ARGs and accelerates the proliferation of Burkholderia. ARG-Rank analysis indicates that the health risk posed by (R)-NAP exposure surpasses that of (S)-NAP, with the highest risk observed when both enantiomers are present. This study elucidates the horizontal transfer and transmission mechanisms of ARGs under chiral NAP stress, underscoring the potential health hazards associated with NAP chiral enantiomers.