In Vitro Antimicrobial Activity of the Novel Antimicrobial Peptide OMN51 Against Multi-Drug-Resistant Pseudomonas aeruginosa Isolated from People with Cystic Fibrosis

Abstract

Background: People with cystic fibrosis (pwCF) frequently suffer from chronic lung infections, with Pseudomonas aeruginosa being the predominant pathogen contributing to disease progression and morbidity. The increasing prevalence of multi-drug-resistant (MDR) P. aeruginosa has diminished treatment options. Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics due to their unique membrane-targeting mechanisms. OMN51, a novel bioengineered AMP derived from capitellacin, was evaluated for antimicrobial activity against P. aeruginosa in sputum samples from pwCF. This study aimed to compare the bactericidal effects of OMN51 with those of a range of conventional antibiotics known to have activity against P. aeruginosa clinical isolates derived from pwCF. Methods:P. aeruginosa clinical isolates were obtained from fifty-six unique sputum cultures of pwCF at a tertiary-university-affiliated hospital. Minimum inhibitory concentrations (MICs) of OMN51 and comparator antibiotics were determined using broth microdilution. Antimicrobial susceptibility was evaluated using the Kirby-Bauer disc diffusion method. Results: OMN51 demonstrated in vitro bactericidal activity across all P. aeruginosa isolates, including MDR strains. MIC values for OMN51 ranged from 4 to 16 µg/mL, with no observed resistance or cross-resistance. Comparative analysis revealed the superior efficacy of OMN51 compared with conventional antibiotics. Conclusions: OMN51 exhibits robust in vitro activity against MDR P. aeruginosa, supporting its candidacy as a therapeutic agent for MDR P. aeruginosa- associated infections. Further studies are warranted to assess pharmacokinetics and in vivo safety and efficacy. OMN51 represents a first-in-class, membrane-targeting therapeutic showing promise against MDR P. aeruginosa.

Keywords: OMN51; Pseudomonas aeruginosa; antibiotics; antimicrobial peptide; bactericidal; cystic fibrosis; in vitro; infections; multi-drug-resistant.

Figure 1

Erythrocyte hemolysis assay. Suspensions of 10% mouse RBCs were exposed to increasing concentrations of OMN51. The positive control group was treated with 2% Tween 20, with the results deemed a reference for 100% hemolysis. After a 1 h incubation, the relative amount of free hemoglobin was assessed as an indication of erythrocyte hemolysis, compared with the free hemoglobin values obtained with the positive control, and presented as a percentage of hemolysis vs. 2% Tween (**** p < 0.0001 for all OMN51 concentrations).