Djenana Vejzovic

Abstract Dynamic changes in lipid membrane composition are a common response to stress, often involving shifts in key lipid molecules. Phosphatidic acid (PA), a central precursor in lipid biosynthesis, accumulates when anionic phospholipid synthesis is blocked—lipids that are typically primary targets of membrane-active antimicrobial peptides (AMPs).

Human cathelicidin LL-37 is a widely studied antimicrobial 37-mer peptide with various ascribed functions, that serves as a template for designing novel peptides. Its derivative, the 24-mer SAAP-148, is highly effective in vitro in eradicating multidrug-resistant bacteria, persistent cells, and biofilms, without inducing resistance. SAAP-148 is characterized by a high cationic charge (+11) and 46% hydrophobicity, which, once the peptide folds into an alpha helix, forms a wide hydrophobic face.

Abstract : OP-145 and SAAP-148, two 24-mer antimicrobial peptides derived from human cathelicidin LL-37, exhibit killing efficacy against both Gram-positive and Gram-negative bacteria at comparable peptide concentrations. However, when it comes to the killing activity against Escherichia coli, the extent of membrane permeabilization does not align with the observed bactericidal activity. This is the case in living bacteria as well as in model membranes mimicking the E.