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Antimicrobials

Supra-structures to target lipid II

Nature Reviews Microbiology volume 22, page 455 (2024)Cite this article

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The global rise of antimicrobial-resistant pathogens is a threat to human health, and new antibiotics are urgently needed to treat infectious diseases. Antimicrobial peptides are host defence molecules that have therapeutic potential owing to their antibiotic activity. Previously, a host defence peptide called plectasin was isolated from the fungus Pseudoplectania nigrella and was shown to exert bactericidal activity against various pathogens. The fungal peptide was shown to target the bacterial cell wall precursor lipid II and to impair cell wall biosynthesis. However, the underlying mechanism of action remains elusive. In this recent study, Breukink, Weingarth and colleagues report that plectasin uses a supramolecular antimicrobial mode of action, whereby the oligomerized peptide sequesters lipid II, a process further enhanced by the binding of calcium to plectasin.

The authors went on to further investigate the lipid II binding interface and showed that plectasin directly interacts with the headgroup of lipid II, which is composed of a pyrophosphate, the sugars N-acetylmuramic acid and N-acetylglucosamine, and a pentapeptide.

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  1. Nature Reviews Microbiology http://www.nature.com/nrmicro/

    Andrea Du Toit

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  1. Andrea Du Toit
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Correspondence to Andrea Du Toit.

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Du Toit, A. Supra-structures to target lipid II. Nat Rev Microbiol 22, 455 (2024). https://doi.org/10.1038/s41579-024-01066-6

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