Evaluated four snake venom-derived cathelicidin-like peptides against multidrug-resistant skin infection pathogens. BotrAMP14 eradicated bacteria within 4 minutes at 1.56 uM, and both BotrAMP14 and CrotAMP14 surpassed meropenem efficacy in vivo while showing no hemolysis up to 128 uM, supporting their potential as topical antimicrobial agents.
Abstract
The growing global threat of antimicrobial resistance (AMR), particularly in cutaneous wound infections, represents a significant clinical and economic challenge. Biofilm formation by multidrug-resistant pathogens, such as, often complicates healing and leads to therapeutic failure. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics due to their potent membrane-disrupting mechanism of action and lower propensity to induce resistance.: This study aimed to evaluate the antibacterial, antibiofilm, and in vivo efficacy of four snake venom-derived cathelicidin-like peptides-Btn (15-34) and BotrAMP14 from, and Ctn (15-34) and CrotAMP14 from-against multidrug-resistant,, andclinical isolates from skin infections, with emphasis on, a WHO priority pathogen.: Minimal Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC), and Minimal Biofilm Inhibitory Concentration (MBIC) were determined against,, and. Time-kill kinetics, hemolytic activity, and cytotoxicity assays were performed. A murine skin wound infection model was established to evaluate in vivo antibacterial efficacy and safety.: MIC/MBC values ranged from 0.78 to 25 µM against planktonic cells. In comparison, MBIC ranged from 1.56 to 12.5 µM against biofilms. BotrAMP14 eradicatedwithin 4 min, while CrotAMP14 achieved bactericidal action in 20 min at 1.56 µM. Both peptides exhibited no hemolytic activity up to 128 µM and low cytotoxicity (IC> 128 µM). In vivo, BotrAMP14 and CrotAMP14 demonstrated significant antibacterial activity at 24 h and 48 h post-infection, respectively, surpassing that of meropenem.: These findings suggest that BotrAMP14 and CrotAMP14 are promising topical antimicrobial agents for managing multidrug-resistant skin infections and may help address the urgent need for alternative therapies against antibiotic-resistant pathogens.
Authors
Cândido, Elizabete de Souza; Buccini, Danieli Fernanda; Miranda, Elizangela de Barros; Gonçalves, Regina Meneses; Brandão, Amanda Loren de Oliveira; Nieto-Marín, Valentina; Leal, Ana Paula Ferreira; Rezende, Samilla Beatriz; Cardoso, Marlon Henrique; Franco, Octavio Luiz