Synthetic Peptides Derived From Lycosa Erythrognatha Venom: Interaction With Phospholipid Membranes and Activity Against Resistant Bacteria

Pablo V M Reis; Vinícius M Lima; Kelton R Souza; Gabriele A Cardoso; Marcella N Melo-Braga; Daniel M Santos; Rodrigo M Verly; Adriano M C Pimenta; Vera Lúcia Dos Santos; Maria Elena de Lima

doi:10.3389/fmolb.2021.680940

Synthetic Peptides Derived From Lycosa Erythrognatha Venom: Interaction With Phospholipid Membranes and Activity Against Resistant Bacteria

Front Mol Biosci. 2021 Jun 8:8:680940. doi: 10.3389/fmolb.2021.680940. eCollection 2021.

Authors

Affiliations

¹ Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo (USP), São Paulo, Brazil.
² Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
³ Departamento de Química, FACET, Universidade Federal dos Vales do Jequitinhonha e Mucuri - Campus JK, Diamantina, Brazil.
⁴ Departamento de Bioquímica e Biologia Molecular, Campos Centro Oeste. Universidade Federal de São João Del-Rei, Diamantina, Brazil.
⁵ Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
⁶ Faculdade Santa Casa de Belo Horizonte, Programa de Pós-Graduação em Medicina - Biomedicina, Belo Horizonte, Brazil.

Abstract

Superbugs are a public health problem, increasing the need of new drugs and strategies to combat them. Our group has previously identified LyeTxI, an antimicrobial peptide isolated from Lycosa erythrognatha spider venom. From LyeTxI, we synthesized and characterized a derived peptide named LyeTxI-b, which has shown significant in vitro and in vivo activity. In this work, we elucidate the interaction of LyeTxI-b with artificial membranes as well as its effects on resistant strains of bacteria in planktonic conditions or biofilms. Isothermal titration calorimetry revealed that LyeTxI-b interacts more rapidly and with higher intensity with artificial vesicles, showing higher affinity to anionic vesicles, when compared to synthetic LyeTxI. In calcein experiments, LyeTxI-b caused greater levels of vesicle cleavage. Both peptides showed antibacterial activity at concentrations of μmol L^-1 against 12 different clinically isolated strains, in planktonic conditions, in a concentration-dependent manner. Furthermore, both peptides elicited a dose-dependent production of reactive oxygen species in methicillin-resistant Staphylococcus aureus. In S. aureus biofilm assay, LyeTxI-b was more potent than LyeTxI. However, none of these peptides reduced Escherichia coli biofilms. Our results show LyeTxI-b as a promising drug against clinically resistant strains, being a template for developing new antibiotics.

Keywords: Lycosa erythrognatha; LyeTxI; LyeTxI-b; LyeTxI/LyeTxI-b interaction with lipidic membranes; antibiotic-resistant; antimicrobial peptide; biofilm.