Phage-Encoded Antimicrobial Peptide gp28 Demonstrates LL-37-Like Antimicrobial Activity Against Multidrug-Resistant Pseudomonas aeruginosa

噬菌体编码的抗菌肽gp28对多重耐药铜绿假单胞菌表现出类似LL-37的抗菌活性

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Abstract

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative bacterial pathogen commonly associated with nosocomial infections. Treatment of P. aeruginosa infections is notoriously difficult due to biofilm formation and antibiotic resistance. Antimicrobial peptides (AMPs) are thought to be promising new antimicrobials. Gp28, a phage-derived AMP, is a novel class of characterized phage AMPs with activity against Escherichia coli in a manner similar to the human peptide LL-37. LL-37 exhibits strong antimicrobial activity against P. aeruginosa as well as biofilm disruption and synergy with certain antibiotics posing the question whether gp28 could act similarly. METHODS: Antibacterial activity of gp28 against P. aeruginosa was established using growth inhibition assays, with minimum inhibitory concentration calculated. Biofilm disruption was assessed using crystal violet staining and scanning electron microscopy. Combined treatment of gp28 with tobramycin against P. aeruginosa was measured using a modified time-kill assay at sublethal concentrations. RESULTS: Gp28 inhibits P. aeruginosa planktonic growth, with a minimum inhibitory concentration of 109 μg mL(-1) and disrupts established biofilms. We demonstrate that gp28 increases the susceptibility of P. aeruginosa to tobramycin. CONCLUSIONS: Gp28 demonstrates potential for development as a putative therapeutic agent against a clinically resistant P. aeruginosa strain either alone or in combination with the frontline antibiotic tobramycin.

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