Antibiotics Promote Escherichia coli-Pseudomonas aeruginosa Conjugation through Inhibiting Quorum Sensing

Abstract

The effect of antibiotics on horizontal gene transfer (HGT) is controversial, and the underlying mechanism remains poorly understood. Here, using <i>Escherichia coli</i> SM10λπ as the donor strain, which carries a chromosomally integrated RP4 plasmid, we investigated the effect of antibiotics on conjugational transfer of a mobilizable gentamicin (Gm) resistance plasmid. The results showed that an exposure to gentamicin that restricted the survival of recipient cells significantly enhanced SM10λπ-<i>Pseudomonas aeruginosa</i> PAO1 conjugation, which was attenuated by a deficiency of <i>lasI-rhlI</i>, genes associated with the generation of the quorum sensing signals <i>N</i>-acyl homoserine lactones (AHLs) in PAO1, or the deletion of the AHL receptor SdiA in SM10λπ. Subsequent mechanistic investigations revealed that a treatment with Gm repressed the mRNA expression of <i>lasI</i> and <i>rhlI</i> in PAO1 and upregulated <i>traI</i> expression in SM10λπ. Moreover, PAO1 treated with other quorum sensing (QS)-inhibiting antibiotics such as azithromycin or chloramphenicol also showed a conjugation-promoting ability. On the other hand, when using non-AHL-producing <i>E. coli</i> strain EC600 as the recipient cells, the promoting effect of Gm on conjugation could not be observed. These data suggest that AHL-SdiA contributes to the effectiveness of antibiotics on plasmid conjugation. Collectively, our findings highlight the HGT-promoting effect of antibiotics and suggest quorum sensing as a promising target for controlling antibiotic resistance dissemination. These findings have implications for assessing the risks of antibiotic use and developing advisable antibiotic treatment protocols.