TY - JOUR
T1 - Antimicrobial Spectrum of Activity and Mechanism of Action of Linear Alpha-Helical Peptides Inspired by Shrimp Anti-Lipopolysaccharide Factors
AU - Matos, Gabriel Machado
AU - Garcia-Teodoro, Beatriz
AU - Martins, Camila Pimentel
AU - Schmitt, Paulina
AU - Guzmán, Fanny
AU - de Freitas, Ana Claudia Oliveira
AU - Stoco, Patricia Hermes
AU - Ferreira, Fabienne Antunes
AU - Stadnik, Marciel João
AU - Robl, Diogo
AU - Perazzolo, Luciane Maria
AU - Rosa, Rafael Diego
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - antibacterial
KW - antifungal
KW - antimicrobial peptide (AMP)
KW - antiparasitic activity
KW - crustacean
KW - cytotoxicity
KW - host defense peptide (HDP)
KW - membrane-disrupting
KW - methicillin-resistant Staphylococcus aureus (MRSA)
KW - synergy
UR - http://www.scopus.com/inward/record.url?scp=85146749144&partnerID=8YFLogxK
U2 - 10.3390/biom13010150
DO - 10.3390/biom13010150
M3 - Article
AN - SCOPUS:85146749144
SN - 2218-273X
VL - 13
JO - Biomolecules
JF - Biomolecules
IS - 1
M1 - 150
ER -