Conjugation inhibitors effectively prevent plasmid transmission in natural environments

Open Access

Abstract

© 2021 Palencia-Gándara et al. ; Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, specifically targeting the plasmid horizontal transfer machinery. However, the in vivo efficiency and the applicability of these compounds to clinical and environmental settings remained untested. Here we show that the synthetic fatty acid 2-hexadecynoic acid (2-HDA), when used as a fish food supplement, lowers the conjugation frequency of model plasmids up to 10-fold in controlled water microcosms. When added to the food for mice, 2-HDA diminished the conjugation efficiency 50-fold in controlled plasmid transfer assays carried out in the mouse gut. These results demonstrate the in vivo efficiency of conjugation inhibitors, paving the way for their potential application in clinical and environmental settings. ; The work performed by the de la Cruz research group was supported by the European Union Seventh Framework Program (FP7-HEALTH-2011-single-stage) "Evolution and Transfer of Antibiotic Resistance" (EvoTAR), grant agreement number 282004. The work performed by C.P.-G. and M.G. was supported by Ph.D. fellowships funded by the University of Cantabria. The work performed by the B.G.-Z. laboratory was supported by The EFFORT project (www.effort-against-amr.eu) FP7-KBBE-2013-7, grant agreement 613754.