The Synthetic Peptide LyeTx I mn∆K, Derived from Spider Toxin, Is Active against Methicillin-Resistant (MRSA) In Vitro and In Vivo.
Fiche publication
Date publication
mars 2024
Journal
Antibiotics (Basel, Switzerland)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
Tous les auteurs :
Vieira APGC, de Souza AN, Lima WG, Brito JCM, Simião DC, Gonçalves LVR, Cordeiro LPB, de Oliveira Scoaris D, Fernandes SOA, Resende JM, Bechinger B, Verly RM, de Lima ME
Lien Pubmed
Résumé
The urgent global health challenge posed by methicillin-resistant (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.
Mots clés
action on membrane, antimicrobial peptides, drug development, multidrug-resistant pathogens, skin infections
Référence
Antibiotics (Basel). 2024 03 8;13(3):