Antimicrobial peptide capsids of de novo design

DOI: 10.1038/s41467-017-02475-3

Authors: Emiliana De Santis (National Physical Laboratory) , Hasan Alkassem (National Physical Laboratory; University College London) , Baptiste Lamarre (National Physical Laboratory) , Nilofar Faruqui (National Physical Laboratory) , Angelo Bella (National Physical Laboratory, UK) , James E. Noble (National Physical Laboratory) , Nicola Micale (Università degli Studi di Messina) , Santanu Ray (University of Brighton) , Jonathan R. Burns (University College London) , Alexander R. Yon (University College London) , Bart W. Hoogenboom (University College London) , Maxim G. Ryadnov (National Physical Laboratory)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 8

State: Published (Approved)
Published: December 2017
Diamond Proposal Number(s): 12739

Abstract: The spread of bacterial resistance to antibiotics poses the need for antimicrobial discovery. With traditional search paradigms being exhausted, approaches that are altogether different from antibiotics may offer promising and creative solutions. Here, we introduce a de novo peptide topology that—by emulating the virus architecture—assembles into discrete antimicrobial capsids. Using the combination of high-resolution and real-time imaging, we demonstrate that these artificial capsids assemble as 20-nm hollow shells that attack bacterial membranes and upon landing on phospholipid bilayers instantaneously (seconds) convert into rapidly expanding pores causing membrane lysis (minutes). The designed capsids show broad antimicrobial activities, thus executing one primary function—they destroy bacteria on contact.

Journal Keywords: Antimicrobials; Protein design; Self-assembly

Subject Areas: Biology and Bio-materials, Medicine


Instruments: B23-Circular Dichroism

Documents:
s41467-017-02475-3.pdf

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