Impacts of Hydrophobic Mismatch on Antimicrobial Peptide Efficacy and Bilayer Permeabilization

• Published in: Antibiotics (Basel) Vol. 12; no. 11; p. 1624
• Main Authors: Meier, Steven, Ridgway, Zachary M, Picciano, Angela L, Caputo, Gregory A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2023
• Subjects: Amino acids; AMP; Analysis; Antibiotics; Antimicrobial agents; Antimicrobial peptides; Antimicrobial resistance; Approximation; Drug resistance; Drug resistance in microorganisms; Effectiveness; Fluorescence; Fluorescence spectroscopy; Health aspects; Health risks; Hydrophobicity; Lipid membranes; Lipids; liposome; membrane destabilization; Membranes; Methicillin; Peptides; Proteins; Public health; Staphylococcus infections; Strains (organisms); fluorescence spectroscopy; membrane destabilization; AMP; liposome
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics12111624

Antimicrobial resistance continues to be a major threat to world health, with the continued emergence of resistant bacterial strains. Antimicrobial peptides have emerged as an attractive option for the development of novel antimicrobial compounds in part due to their ubiquity in nature and the general lack of resistance development to this class of molecules. In this work, we analyzed the antimicrobial peptide C18G and several truncated forms for efficacy and the underlying mechanistic effects of the sequence truncation. The peptides were screened for antimicrobial efficacy against several standard laboratory strains, and further analyzed using fluorescence spectroscopy to evaluate binding to model lipid membranes and bilayer disruption. The results show a clear correlation between the length of the peptide and the antimicrobial efficacy. Furthermore, there is a correlation between peptide length and the hydrophobic thickness of the bilayer, indicating that hydrophobic mismatch is likely a contributing factor to the loss of efficacy in shorter peptides.