Antimicrobial Spectrum of Activity and Mechanism of Action of Linear Alpha-Helical Peptides Inspired by Shrimp Anti-Lipopolysaccharide Factors

Biomolecules. 2023 Jan 11;13(1):150. doi: 10.3390/biom13010150.

Abstract

Shrimp antilipopolysaccharide factors (ALFs) form a multifunctional and diverse family of antimicrobial host defense peptides (AMPs) composed of seven members (groups A to G), which differ in terms of their primary structure and biochemical properties. They are amphipathic peptides with two conserved cysteine residues stabilizing a central β-hairpin that is understood to be the core region for their biological activities. In this study, we synthetized three linear (cysteine-free) peptides based on the amino acid sequence of the central β-hairpin of the newly identified shrimp (Litopenaeus vannamei) ALFs from groups E to G. Unlike whole mature ALFs, the ALF-derived peptides exhibited an α-helix secondary structure. In vitro assays revealed that the synthetic peptides display a broad spectrum of activity against both Gram-positive and Gram-negative bacteria and fungi but not against the protozoan parasites Trypanosoma cruzi and Leishmania (L.) infantum. Remarkably, they displayed synergistic effects and showed the ability to permeabilize bacterial membranes, a mechanism of action of classical AMPs. Having shown low cytotoxicity to THP-1 human cells and being active against clinical multiresistant bacterial isolates, these nature-inspired peptides represent an interesting class of bioactive molecules with biotechnological potential for the development of novel therapeutics in medical sciences.

Keywords: antibacterial; antifungal; antimicrobial peptide (AMP); antiparasitic activity; crustacean; cytotoxicity; host defense peptide (HDP); membrane-disrupting; methicillin-resistant Staphylococcus aureus (MRSA); synergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Anti-Infective Agents* / chemistry
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Gram-Negative Bacteria
  • Gram-Positive Bacteria
  • Humans
  • Lipopolysaccharides / pharmacology
  • Microbial Sensitivity Tests
  • Protein Conformation, alpha-Helical

Substances

  • Anti-Bacterial Agents
  • Lipopolysaccharides
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides