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

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.

PEGylation of the antimicrobial peptide LyeTx I-b maintains structure-related biological properties and improves selectivity

“…Likewise, the same PEG-induced spatial impairment can be the cause of a smaller lytic activity for LyeTx I-bPEG, as evidenced by its smaller calcein release percentage. Nevertheless, the interaction mechanism of LyeTx I-b, mainly driven by electrostatic forces ( Reis et al, 2021 ), does not seem to be significantly altered after PEGylation, since a smaller calcein release was observed for both peptides in the presence of zwitterionic LUVs in comparison with anionic LUVs.…”

“…In this context, the search for novel antimicrobial agents against superbugs is an urgent need, and antimicrobial peptides (AMPs) stand out from their conventional counterparts due to their bactericidal potential, anti-inflammatory activity, and modulation of the immune system ( Kang et al, 2012 ; Fosgerau and Hoffmann, 2015 ; Zhang and Gallo, 2018 ; Chen and Lu, 2020 ). Fungal and bacterial cell membrane phospholipids are known targets for these biopolymers, which act by increasing permeability, leading to leakage of intracellular material and subsequent death of the microorganism ( Brito et al, 2021 ; Reis et al, 2021 ).…”

LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model

“…LyeTx I-b is a synthetic peptide differing from LyeTx I by lacking a cysteine residue at position 16. LyeTx I-b was active against diverse bacteria in in vitro and in vivo assays [ 35 , 36 , 37 ] and presented a higher affinity in phospholipid membrane assays compared to LyeTx I [ 38 ]. Furthermore, a previous study conducted by our group showed that intraocular injection of LyeTx I-b suppressed neovascularization in ocular disease using a chorioallantoic membrane model [ 39 ].…”