Polyunsaturated fatty acids (PUFAs) amplify the killing effect of peptide antibiotics in Aeromonas hydrophila

Presenter(s)

Meredith Grant

Abstract or Description

One of the top global threats to public health is antimicrobial resistance. There is an urgent need for development of novel therapeutic regimens that can bypass existing microbial mechanisms of antibiotic resistance. Previous research has established that exogenous polyunsaturated fatty acids (PUFAs) are assimilated into the membrane phospholipids of gram-negative bacteria, thereby altering membrane permeability and susceptibility to antimicrobials. Introducing membrane vulnerability may create opportunities for antimicrobials to diffuse through the outer and inner membrane of gram-negative bacteria. In this study, combinatorial treatment of the human pathogen Aeromonas hydrophilia with seven PUFAs (linoleic acid [18:2], alpha- linolenic acid [18:3a], gamma-linolenic acid [18:3g], dihomo-gamma-linolenic acid [20:3], arachidonic acid [20:4], eicosapentaenoic acid [20:5], docosahexaenoic acid [22:6]) and 4 antimicrobials (polymyxin B, colistin, ampicillin, and imipenem) was evaluated using broth dilution minimum inhibitory concentration (MIC) assays. Significant changes in MIC were observed, particularly with the cyclic peptides polymyxin B and colistin, wherein most PUFAs significantly lowered the MIC by a range of 4 - 64-fold. Minimal changes to MIC were observed for ampicillin and imipenem, antibiotics that access bacteria through a protein-mediated process. Collectively, this data highlights not only PUFA-mediated bio membrane effects, but also the potential for PUFAs and membrane-attacking antimicrobials to synergistically target gram- negative infections.

Mentor

David Giles