Murepavadin is a novel peptide antibiotic that exhibits potent antibiofilm activity and enhances the efficacy of conventional antibiotics against Pseudomonas aeruginosa

Abstract

Abstract Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are difficult to treat due to biofilm formation. This study evaluates the antimicrobial and antibiofilm efficacy of murepavadin (MUR), a novel peptidomimetic targeting the LptD protein, alone and combined with conventional antibiotics against clinical isolates. The minimum inhibitory concentrations (MICs) of 50 isolates against MUR and five antibiotics were determined. Synergy in planktonic cultures was assessed by checkerboard assays. For biofilm, the Bliss independence model was applied using MBIC (minimum biofilm inhibitory concentration) and the concentration yielding ≥90% biomass reduction, as measured by crystal violet (CV) staining. MUR showed potent activity against planktonic cells (MIC50/90: 0.25/0.5 mg l–1). Synergy tests revealed consistent MUR-colistin synergy across all strains, with notable interactions against carbapenemase-producers when combined with meropenem. In biofilms, MUR demonstrated significantly lower MBIC and lower concentrations required for ≥90% biomass reduction (CV staining). Bliss analysis confirmed strong synergistic biofilm inhibition in all combinations, most pronounced with tobramycin. MUR exhibits high efficacy against both planktonic and biofilm-forming MDR P. aeruginosa. Its synergy with colistin and tobramycin highlights its potential as a strategic combination partner.