Antidepressants promote the spread of extracellular antibiotic resistance genes via transformation

The development of antibiotic resistance as an unavoidable consequence of the application of antimicrobials is a significant concern for human health. Antidepressants are being increasingly consumed globally. Human gut microbial communities are frequently exposed to antidepressants, yet little is known about the interaction between antidepressants and antibiotic resistance. This study aimed to investigate whether antidepressants can accelerate the dissemination of antibiotic resistance by increasing the rate of the horizontal transfer of antibiotic resistance genes (ARGs). Results demonstrated that some of the commonly-prescribed antidepressants (Duloxetine, Sertraline, Fluoxetine and Bupropion) at clinically relevant concentrations can significantly (n = 9; Padj < 0.01) promote the transformation of extracellular ARGs into Acinetobacter baylyi ADP1 for a maximum of 2.3-fold, which is primarily associated with the overproduction of reactive oxygen species. The increased cell membrane permeability and porosity, stimulated transcription and translation of competence, SOS response, universal stress response and ATP synthesis-related genes are also associated with antidepressants-enhanced transformation. This study demonstrated that some antidepressants can speed up the spread of antibiotic resistance by promoting the transformation of ARGs, which emphasizes the necessity to assess the potential risks of antidepressants in spreading antibiotic resistance during clinical antidepressant applications.