Abstract
The structure–activity relationships and mode of action of synthesized glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-related antimicrobial peptides were investigated. Including the native skipjack tuna GAPDH-related peptide (SJGAP) of 32 amino acid residues (model for the study), 8 different peptide analogs were designed and synthesized to study the impact of net charge, hydrophobicity, amphipathicity, and secondary structure on both antibacterial and antifungal activities. A net positive charge increase, by the substitution of anionic residues or C-terminal amidation, improved the antimicrobial activity of the SJGAP analogs (minimal inhibitory concentrations of 16–64 μg/mL), whereas the alpha helix content, as determined by circular dichroism, did not have a very definite impact. The hydrophobicity of the peptides was also found to be important, especially for the improvement of antifungal activity. Membrane permeabilization assays showed that the active peptides induced significant cytoplasmic membrane permeabilization in the bacteria and yeast tested, but that this permeabilization did not cause leakage of 260 nm-absorbing intracellular material. This points to a mixed mode of action involving both membrane pore formation and targeting of intracellular components. This study is the first to highlight the links between the physicochemical properties, secondary structure, antimicrobial activity, and mechanism of action of antimicrobial peptides from scombrids or homologous to GAPDH.
Highlights
It is well-documented that the massive use of traditional antibiotics for the treatment of diseases caused by different pathogenic microorganisms promotes the development of multi-drug resistant microorganisms that are capable of resisting several different antibiotics
Antimicrobial peptides (AMPs), which can be defined as small peptide molecules, generally composed of 7 to 100 amino acids that show inhibitory activity against microorganisms, represent a very promising avenue in the search for alternative molecules to conventional antibiotics
The antibacterial activity of a small peptide from a hydrolysate of Atlantic mackerel, named AMGAP, has been demonstrated [38]. This peptide is homologous to two other antimicrobial peptides (AMPs) that were studied by Seo et al, namely Yellowfin Tuna GAPDH-related antimicrobial peptide (YFGAP) [39] and skipjack tuna GAPDH-related peptide (SJGAP) [40]
Summary
Numerous studies conducted on these AMPs have shown that they most often act by destabilizing microbial membranes, notably by permeabilizing them, as evidenced by some reviews and articles written on this subject [2,3,4]. These mechanisms are generally not dependent on specific receptors, reducing the risks of resistance development and increasing the therapeutic potential of these molecules [5,6,7,8,9]. This certainly explains why AMPs have been the subject of so much research in recent years; between 2012 and
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