Exploring the effects of fatty acids (PUFAs) on the antimicrobial resistance in Vibrio cholerae

As antibiotic resistance becomes a major challenge for public health professionals, our research objectives aimed to investigate the potential for polyunsaturated fatty acids (PUFAs) to create membrane vulnerability in the gram-negative pathogen Vibrio cholerae to help improve the efficacy of several antibiotics. V. cholerae, normally residing in aquatic environments, is capable of altering its phospholipid composition through the uptake and assimilation of exogenous polyunsaturated fatty acids. The purpose of this study was to measure PUFA-mediated changes in the membrane permeability and antibiotic resistance of Vibrio cholerae. The three physiologically relevant PUFAs used were linoleic acid [18:2], arachidonic acid [20:4], and docosahexaenoic acid [22:6]). Bacterial membrane permeability was measured using a crystal violet assay with each PUFA resulting in at least a 10% change in uptake of the dye. When the cyclic peptides polymyxin B (PMB) and colistin were administered at subinhibitory concentrations, PUFA-specific permeability trends were observed. The availability of PUFAs caused significant changes to the minimum inhibitory concentrations (MICs) of PMB, colistin, LL-37, and Cecropin A. Strikingly, PMB and colistin were found to decrease the MIC by at least 4-fold. Not only did 18:2, 20:4, and 22:6 alter bacterial permeability, but they also induced vulnerability to PMB and colistin in V. cholerae, perhaps suggesting synergistic potential in the control and prevention of pathogens. 18:2 did not affect MICs of LL-37 and Cecropin A whereas, the addition of 20:4 and 22:6 increased the MICs by at least 2-fold