Aggregation and Water-Membrane Partition as Major Determinants of the Activity of the Antibiotic Peptide Trichogin GA IV

Abstract

Water-membrane partition and aggregation behavior are fundamental aspects of the biological activity of antibiotic peptides, natural compounds causing the death of pathogenic organisms by perturbing the permeability of their membranes. A synthetic fluorescent analog of the natural lipopeptaibol trichogin GA IV was used to study its interaction with model membranes. Time-resolved fluorescence data show that in water, an equilibrium between monomers and small aggregates is present, the two species having different affinity for membranes. Therefore, association curves are strongly dependent on peptide concentration. A similar heterogeneity is present in the membrane phase, which strongly suggests the occurrence of a monomer-aggregate equilibrium in this case, too. The relative population of each species was determined and a strong correlation between the concentration of membrane-bound aggregates and membrane leakage was found, thereby suggesting that liposome perturbation is due to peptide aggregates only. Light-scattering measurements demonstrate that leakage is not due to liposome micellization. Moreover, experiments with markers of different sizes show that molecules with a diameter of approximately 4 nm are released only to a minor extent. Overall, these results suggest that, within the concentration range explored, pore formation by peptide aggregates is the most likely mechanism of action for trichogin in membranes.

Esculentin‐1b(1–18) – a membrane‐active antimicrobial peptide that synergizes with antibiotics and modifies the expression level of a limited number of proteins in Escherichia coli

“…Taken together, these observations are in line with those made above using intact cells (Figs 5 and 6), and are consistent with the suggestion that Esc(1-18) binds and destabilizes the bacterial membrane, but to a lesser extent than temporin-1Tl [37]. According to what has been stated for other antimicrobial peptides [38], such a discrepancy between the two frog skin peptides might be related to a higher fraction of membranebound active temporin-1Tl than of Esc (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Fig.…”

Electrostatic Association of Glutathione Transferase to the Nuclear Membrane

“…Large unilamellar vesicles (LUVs) were prepared according to a procedure reported previously (22). Briefly, lipids were dissolved in a chloroform/ methanol solution (1:1 v/v), and the solvents were evaporated under reduced argon atmosphere until a thin film formed.…”

Fluorescence spectroscopy and molecular dynamics simulations in studies on the mechanism of membrane destabilization by antimicrobial peptides

“…In all cases in which the natural peptide is modified, it is important to check that the labels do not perturb its behavior (e.g., by comparing its membrane-perturbing activity to that of the natural peptide) [20,64].…”