The antimicrobial peptide lugdunin forms channels in bacterial membranes

The global health community is increasingly alarmed by the rise of antibiotic-resistant bacteria. These resilient strains pose significant threats to public health, leading to infections that are difficult to treat with conventional antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) is a prime example, known for causing severe infections in hospitals and communities alike. The urgent need for novel antimicrobial agents has never been more critical. To address this, scientists have turned their attention to natural sources, particularly the human microbiome, as a potential treasure trove of new antibiotics.

One such novel antibiotic is lugdunin, an antimicrobial peptide produced by the nasal and skin commensal bacterium Staphylococcus lugdunensis. This cyclo-heptapeptide has demonstrated potent antimicrobial activity against a broad spectrum of Gram-positive bacteria, including the notorious MRSA. However, the precise mode of action of lugdunin remained elusive, prompting further investigation into its potential as a new class of antibiotics.

A recent study, published in Nature Communications, unraveled how lugdunin exerts its antimicrobial effects.

Researchers revealed that lugdunin partitions strongly into lipid compositions that resemble Gram-positive bacterial membranes but much less so into those containing eukaryotic membrane cholesterol.

Upon insertion into the bacterial membrane, lugdunin forms peptide nanotubes that facilitate the translocation of protons and monovalent cations across the membrane, dissipating the bacterial membrane potential, and effectively killing the bacteria.

Single-channel recordings performed with the Orbit 16 bilayer recording station confirmed lugdunin’s channel activity with characteristics similar to gramicidin A (GK+ ≈ 29 pS, pore diameter close to 4 Å).

Overall, by elucidating the mechanism by which lugdunin disrupts bacterial membranes, researchers have laid the groundwork for developing new antimicrobial agents based on this peptide.

Find the original article here: https://www.nature.com/articles/s41467-024-47803-6

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