Characterization of Antimicrobial Peptide WAM-1 and its Interactions with Clinical Isolates of Acinetobacter baumannii

Acinetobacter baumannii, a prominent nosocomial pathogen, commonly causes life-threatening disease in immunocompromised individuals with mortality rates approaching 35%. Known for its multidrug resistance, studies investigating antimicrobial peptides (AMPs) have proven promising. We have previously shown that the AMP WAM-1 exhibits potent bactericidal activity against A. baumannii, but its full therapeutic value and mechanism of action have not yet been elucidated. To evaluate potential clinical relevance of WAM-1, we characterized its antibacterial effects, inhibition by lipopolysaccharide (LPS), and whether treatment with WAM-1 induced resistance in A. baumannii. Additionally, we explored WAM-1’s mechanism of action by visualizing structural changes induced by treatment with WAM-1 and evaluating permeabilization of the bacterial outer membrane. The activity of WAM-1 was comparable to that of efficacious antibiotics and was not inhibited by the presence of exogenous LPS. Scanning electron microscopy showed evidence of membrane disruption, cellular content leakage, and cell lysis, indicating damage to the bacterial outer membrane, and depolarization of the membrane was observed. WAM-1 was found to induce resistance more slowly than tested antibiotics. Overall, our data indicates that WAM-1 may be a promising therapeutic option for A. baumannii infections and may act, at least in part, by damaging the outer membrane.