RESISTANCE-AWARE SPECTRUM PROFILING OF ANTIMICROBIAL PEPTIDES AGAINST PRIORITY BACTERIAL PATHOGENS

Abstract

Antimicrobial resistance increasingly compromises the effectiveness of conventional antibacterial therapy, creating a need for alternative agents capable of maintaining activity against resistant pathogens. This study evaluated antimicrobial peptides (AMPs) using a resistance-aware spectrum-profiling framework integrating physicochemical characteristics, minimum inhibitory concentration (MIC), hemolytic activity, and selectivity. A total of 225 AMP–pathogen observations covering six priority bacterial pathogens were analyzed. Resistance profiles were classified as susceptible, multidrug-resistant (MDR), or extensively drug-resistant (XDR). Statistical comparisons were performed in Python using the Kruskal–Wallis H test. Peptides exhibited substantial physicochemical and antimicrobial heterogeneity, with MIC values ranging from 0.43 to 104.30 µM. Pathogen-specific MIC distributions did not differ significantly (p = 0.439), despite numerical variation among bacterial species. In contrast, resistance phenotype was significantly associated with AMP potency (p = 0.004). Mean MIC increased from 10.04 µM in susceptible profiles to 14.69 µM in MDR and 26.04 µM in XDR profiles. Selectivity declined concurrently from 22.03 to 9.05, whereas hemolytic activity remained comparatively stable. These findings indicate that resistance phenotype provides an important dimension for interpreting AMP performance beyond pathogen identity alone. Integrating antimicrobial potency with resistance status and selectivity may support more informative prioritization of peptide candidates for subsequent experimental evaluation.