Membrane adaptation limitations inEnterococcus faecalisunderlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

Abstract

COEs are emerging antimicrobials to combat drug resistant infections and to which bacteria develop only limited resistance.

Enterococcus faecalis Adapts to Antimicrobial Conjugated Oligoelectrolytes by Lipid Rearrangement and Differential Expression of Membrane Stress Response Genes

“…N,hexyl)amino)-styryl)benzene tetraiodide] and COE1-3Py [1,4-bis(4 -(N,N-bis(6 -(pyridinium)hexyl)amino)-styryl)benzene tetraiodide] inhibit E. faecalis OG1RF at 2 µM and 1 µM, respectively. In a previous study, serial passaging of E. faecalis with either COE produced strains EFC3C and EFC3Py with an increase of 4-and 16-fold in their resistance to COE1-3C and COE1-3Py, respectively, in comparison to the parental strain (Chilambi et al, 2018). Whole genome sequencing of EFC3C and EFC3Py revealed mutations in the liaFSR three-component signal transduction system (Chilambi et al, 2018).…”

“…In a previous study, serial passaging of E. faecalis with either COE produced strains EFC3C and EFC3Py with an increase of 4-and 16-fold in their resistance to COE1-3C and COE1-3Py, respectively, in comparison to the parental strain (Chilambi et al, 2018). Whole genome sequencing of EFC3C and EFC3Py revealed mutations in the liaFSR three-component signal transduction system (Chilambi et al, 2018). Quantification of the membrane fatty acid composition of the resistant strains showed significant changes in the cis-vaccenic acid and cyclopropane fatty acids in their membranes (Chilambi et al, 2018).…”

“…Conjugated oligoelectrolytes (COEs) (shown in Table 1) are characterized by a π-conjugated aromatic backbone with terminal ionic pendant groups (Thomas et al, 2013). They are amphipathic and are active against a range of pathogens, which includes both gram types, fungi and drug resistant strains (Chilambi et al, 2018). COEs are primarily thought to be membrane acting because they spontaneously intercalate with, and appear to reside in, the lipid bilayer because of their amphiphilic nature (Hinks et al, 2015).…”

“…Whole genome sequencing of EFC3C and EFC3Py revealed mutations in the liaFSR three-component signal transduction system (Chilambi et al, 2018). Quantification of the membrane fatty acid composition of the resistant strains showed significant changes in the cis-vaccenic acid and cyclopropane fatty acids in their membranes (Chilambi et al, 2018). These fatty acids were directly implicated in COE resistance in E. faecalis through a supplementation study (Chilambi et al, 2018) but they did not explain COE resistance in its entirety.…”

“…Quantification of the membrane fatty acid composition of the resistant strains showed significant changes in the cis-vaccenic acid and cyclopropane fatty acids in their membranes (Chilambi et al, 2018). These fatty acids were directly implicated in COE resistance in E. faecalis through a supplementation study (Chilambi et al, 2018) but they did not explain COE resistance in its entirety. To identify additional factors, which could contribute to this resistance, transcriptomic studies on the response of E. faecalis wild type, EFC3C and EFC3Py to COEs were undertaken.…”