Linoleic acid and α‐linolenic acid inhibit conjugative transfer of an IncX4 plasmid carryingmcr‐1

Abstract

Aims The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. Methods and Results Two unsaturated fatty acids, linoleic acid (LA) and α‐linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l−1, respectively, were used to assess the effects on conjugative transfer of a mcr‐1‐harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT‐PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose‐dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11‐like genes among over 37 classes of plasmids originated from both Gram‐negative and Gram‐positive bacteria. Conclusions This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. Significance and Impact of the Study Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

Short-chain fatty acids inhibit bacterial plasmid transfer through conjugation in vitro and in ex vivo chicken tissue explants

“…These data indicate that SCFAs do have a universal mechanism of action for inhibiting plasmid conjugation outside of targeting specific genes. This may be different than what was previously observed with medium-chain PUFAs or may be additive and provide a synergistic outcome ( Li et al, 2021 ).…”

“…With the emergence and spread of MDR plasmids, a new emphasis on non-antibiotic therapeutics for managing the microbiome associated with humans and animals has been developed ( Fernandez-Lopez et al, 2005 ; Solis-Cruz et al, 2020 ; Cabezn et al, 2017 ; Lopatkin et al, 2017 ; Zhang et al, 2019 ; Li et al, 2021 ). Inhibition of bacterial plasmid transfer, as opposed to indiscriminately eliminating bacterial hosts, is a desirable approach to preventing the spread of MDR plasmids.…”

“…On such approach involves the use of dietary additives, such as the PUFAs linoleic acid and alpha-linolenic acid, which have been briefly demonstrated as conjugation inhibitors (COINs) ( Li et al, 2021 ). However, the application of this novel dietary intervention has not yet been shown in host-associated conditions.…”