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Rajamani Lakshminarayanan, Eunice Goh Tze Leng, Liu Shouping, Roger Beuerman; Cationic Branched Peptides as Antibiotic Adjuvants. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2466.
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The purpose of this study is to investigate the efficacy of a series of branched peptides in increasing the potency of aminoglycosides and fluorquinolones against multi-drug resistant Gram-negative pathogens.
The outer membrane (OM) permeability and affinity for lipopolysaccharides (LPS) were determined by N-1-phenyl naphthylamine, Bodipy-TR cadevarine assays and isothermal titration calorimetry. The fractional inhibitory concentration index (FICI) was determined by checker board assay. Finally, the antibiotic adjuvant capacity of the most efficacious peptides was determined by bacterial viability assays.
Branched peptides carrying two copies of the putative sequence RGRKX1X2X3X4 or RGX1X2X3X4RR, where X1-X4 are natural or unnatural amino acid residues were synthesized and their antimicrobial properties and their ability to permeabilize the OM of P. aeruginosa were determined. When compared to the parent peptide B2088, the newly designed peptides displayed weak antimicrobial properties but superior ability to potentiate the antimicrobial activities of chloramphenicol, aminoglycosides (gentamycin and tobramycin) and fluoroquinolones (moxifloxacins and levofloxacin) as confirmed by checker board assays. To determine the efficacy, bacterial viability was determined for antibiotic eye drop solutions (Tobrex and gentamycin) in 10-fold serial dilutions with or without the adjuvants. Addition of mM concentrations of the peptides to 10-5 × diluted commercially available antibiotics solutions caused >3 log10 decrease in bacterial viability when compared to antibiotics alone. These results suggest that the peptides potentiate the antimicrobial efficacy of antibiotic eye drops as well.
The results showed that cationic branched peptides which lacks potent antimicrobial activity can be used as adjuvants that can potentiate the antimicrobial efficacies of commercial eye drop medications.
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