Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

In Vivo and In Vitro Evaluation of the Antibacterial Activity of the Synthetic Peptide LyeTx I mn∆K, Derived From Lycosa erythrognatha Spider Toxin, Against Methicillin-Resistant Staphylococcus aureus (MRSA)

Ana Paula Gonçalves Coelho Vieira
,
Amanda Neves De Souza
ORCID logo ,
William Gustavo Lima
ORCID logo ,
Julio Cesar Moreira Brito
,
Daniela Carolina Simião
ORCID logo ,
Lucas Vinicius Ribeiro Gonçalves
ORCID logo ,
Lídia Pereira Barbosa Cordeiro
,
Denise de Oliveira Scoaris
,
Simone Odília Antunes Fernandes
,
Jarbas Magalhães Resende
,
Burkhard Bechinger
ORCID logo ,
Rodrigo Moreira Verly
* ,
Maria Elena De Lima
*
Version 1 : Received: 29 January 2024 / Approved: 30 January 2024 / Online: 30 January 2024 (05:00:30 CET)

A peer-reviewed article of this Preprint also exists.

Vieira, A.P.G.C.; de Souza, A.N.; Lima, W.G.; Brito, J.C.M.; Simião, D.C.; Gonçalves, L.V.R.; Cordeiro, L.P.B.; de Oliveira Scoaris, D.; Fernandes, S.O.A.; Resende, J.M.; Bechinger, B.; Verly, R.M.; de Lima, M.E. The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo. Antibiotics 2024, 13, 248. Vieira, A.P.G.C.; de Souza, A.N.; Lima, W.G.; Brito, J.C.M.; Simião, D.C.; Gonçalves, L.V.R.; Cordeiro, L.P.B.; de Oliveira Scoaris, D.; Fernandes, S.O.A.; Resende, J.M.; Bechinger, B.; Verly, R.M.; de Lima, M.E. The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo. Antibiotics 2024, 13, 248.

Abstract

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (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 Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing some 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 demonstrating remarkable efficacy against planktonic cells and biofilms of MRSA, 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 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, was showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wound in mice. Together the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Keywords

Antimicrobial peptides; Methicillin-resistant Staphylococcus aureus (MRSA); Lycosa erythrognatha; Skin infections; Action on membrane.

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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