Pseudonajide peptide derived from snake venom alters cell envelope integrity interfering on biofilm formation in Staphylococcus epidermidis

Rafael Schneider,Sylvie Nonin-Lecomte,Sophie Chat,Reynald Gillet,Muriel Primon-Barros,Alexandre José Macedo,Rafael Gomes Von Borowski

doi:10.1186/s12866-020-01921-5

Abstract

BackgroundThe increase in bacterial resistance phenotype cases is a global health problem. New strategies must be explored by the scientific community in order to create new treatment alternatives. Animal venoms are a good source for antimicrobial peptides (AMPs), which are excellent candidates for new antimicrobial drug development. Cathelicidin-related antimicrobial peptides (CRAMPs) from snake venoms have been studied as a model for the design of new antimicrobial pharmaceuticals against bacterial infections.ResultsIn this study we present an 11 amino acid-long peptide, named pseudonajide, which is derived from a Pseudonaja textilis venom peptide and has antimicrobial and antibiofilm activity against Staphylococcus epidermidis. Pseudonajide was selected based on the sequence alignments of various snake venom peptides that displayed activity against bacteria. Antibiofilm activity assays with pseudonajide concentrations ranging from 3.12 to 100 μM showed that the lowest concentration to inhibit biofilm formation was 25 μM. Microscopy analysis demonstrated that pseudonajide interacts with the bacterial cell envelope, disrupting the cell walls and membranes, leading to morphological defects in prokaryotes.ConclusionsOur results suggest that pseudonajide’s positives charges interact with negatively charged cell wall components of S. epidermidis, leading to cell damage and inhibiting biofilm formation.

Highlights

The increase in bacterial resistance phenotype cases is a global health problem
The peptide possesses antimicrobial and antibiofilm activity against S. epidermidis, and our results suggest that it acts on this bacteria’s cell wall and membrane components quite quickly and at low doses
The alignment of snake sequences (Naja atra - Cathelicidin NA-CATH; Bothrops atrox - Batroxicidin; Crotalus durissus terrificus - Crotalicidin; Pseudonaja textilis - Cathelicidin Pt_CRAMP1; Ophiophagus hannah - Cathelicidin OH-CATH; Ophiophagus hannah - Cathelicidin OH-CATH30, and; Bungarus fasciatus - Cathelicicin-BF) revealed a greater number of conserved motifs among snake peptides than that found in other groups

Summary

Introduction

The increase in bacterial resistance phenotype cases is a global health problem. New strategies must be explored by the scientific community in order to create new treatment alternatives. Animal venoms are complex mixtures of inorganic salts, small organic molecules, high-molecular-weight proteins including enzymes, and peptides, used for both protection and predation [2, 3]. Because they are both potent and specific in their interactions with the cell wall and membrane components of different cells, venom constituents are attractive candidates for the development of novel therapeutics and pesticides [4], they remain largely unexplored. AMPs have complex and wideranging mechanisms of action They can directly target bacterial membranes, damaging cell integrity and causing osmotic imbalance. Due to this complexity and the widescale of their target interactions, resistance to such molecules seems to arise less commonly than with conventional antibiotics [6]

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