A Bioinspired Mastoparan Exhibits Concentration-Dependent Anti-Bacterial Activity via Membrane Disruption

TL;DR

A wasp venom-inspired peptide disrupts bacterial membranes in a concentration-dependent way, showing quick and strong antibacterial effects.

Contribution

The study reveals the physicochemical mechanism of a bioinspired mastoparan's membrane-disrupting activity and its antimicrobial effects.

Findings

Mast-MO disrupts lipid membranes through surface activity in a concentration-dependent manner.

Changes in ionic strength and pH reduce mast-MO adsorption to membranes.

Mast-MO shows rapid and potent antibacterial activity against E. coli within 15 minutes.

Abstract

Antimicrobial peptides are widely investigated in the
literature,
but their mechanism of action and effects on lipid membranes are not
completely understood from a physicochemical perspective. In this
study, we employed a bioinspired mastoparan from wasp venom, mast-MO,
and characterized its interactions with model lipid membranes, either
as a supported lipid bilayer or as free-standing vesicles in solution.
An array of complementary physicochemical characterization techniques
was employed to study the surface activity of the peptide alone and
how its adsorption affects lipid membrane properties in terms of lateral
organization and integrity. We found that peptide action is related
to its intrinsic surface activity, resulting in disrupted lipid packing
of supported membranes and vesicles via a concentration-dependent
mechanism. Changing solution conditions, e.g., ionic strength and
pH, altered the electrostatic interactions between the membrane and
mast-MO, resulting in less significant adsorption. This mechanism
of action was also validated in vitro for Gram-negative E. coli bacteria, demonstrating rapid action (within
15 min) and potent antimicrobial activity. These results provide new
information on the molecular effects of mastoparan’s interactions
with membranes.

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