Work

Antimicrobial peptide mechanism of action on S. aureus membranes determined by in vivo solid-state NMR

Year: 2025

Type: article

Abstract: Staphylococcus aureus (S. aureus) is a Gram-positive pathogenic bacterium and a major cause of nosocomial infections. Between 20 % and 50 % of S. aureus strains are resistant to a wide range of antibiotics. DMS-DA6-NH 2 (DA6) is a novel antimicrobial peptide (AMP) that exhibits high efficacy against various bacterial strains, particularly S. aureus , by disrupting its membrane through an as-yet-unknown mechanism. We employed in vivo 2 H solid state Nuclear Magnetic Resonance (NMR) to investigate the mode of action of AMPs on deuterated bacteria. This technique provides insights into membrane order and its changes with increasing AMP concentration. Our results enabled us to compare the mechanism of DA6 with those of AMPs with established modes of action. We found that DA6 induces pore formation in the membrane of S. aureus. This protocol serves as a template for determining the mechanisms of action of other peptides, an essential step for developing and patenting such drugs for the treatment of human diseases. • DMS-DA6 is a promising antibacterial peptide, alternative to antibiotics. • Solid-state NMR can help elucidate the mechanism of action of peptides in vivo. • Minimal bactericidal concentrations are measured at high bacterial densities. • The mechanisms of three peptides against Staphylococcus aureus are determined. • DMS-DA6 functions as a pore-forming antimicrobial peptide.

Source: Biophysical Chemistry

DOI: 10.1016/j.bpc.2025.107532

Authors: Laila Zaatouf, Thierry Drujon, Astrid Walrant, Emmanuelle Sachon, Dror E. Warschawski

Institutions: Centre National de la Recherche Scientifique, Université Paris Sciences et Lettres, École Normale Supérieure - PSL, Sorbonne Université, Chimie Physique et Chimie du Vivant

Language: English

Topic: Antimicrobial Peptides and Activities

Subfield: Microbiology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,720