Journal article

How do Self-Assembling Antimicrobial Lipopeptides Kill Bacteria?

Haoning Gong, Marc-Antoine Sani, Xuzhi Hu, Ke Fa, Jack William Hart, Mingrui Liao, Peter Hollowell, Jessica Carter, Luke A Clifton, Mario Campana, Peixun Li, Stephen M King, John RP Webster, Armando Maestro, Shiying Zhu, Frances Separovic, Thomas A Waigh, Hai Xu, Andrew J McBain, Jian Ren Lu

ACS Applied Materials & Interfaces | AMER CHEMICAL SOC | Published : 2020

Abstract

Antimicrobial peptides are promising alternatives to traditional antibiotics. A group of self-assembling lipopeptides was formed by attaching an acyl chain to the N-terminus of α-helix-forming peptides with the sequence C x -G(IIKK) y I-NH2 (C x G y , x = 4-12 and y = 2). C x G y self-assemble into nanofibers above their critical aggregation concentrations (CACs). With increasing x, the CACs decrease and the hydrophobic interaction..

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Grants

Awarded by Marie Curie Fellowship ITN grant under SNAL (small nano-objects for alteration of lipid bilayers)


Awarded by AstraZeneca


Funding Acknowledgements

The authors would like to thank the University of Manchester for overseas research studentships to H.G., K.F., and X.H., the China Scholarship Council for studentships to H.G. and M.L., and BBSRC for a studentship to J.C. We also gratefully acknowledge research funding awarded to X.H. from Syngenta, to K.F. from the Science and Technology Facilities Council, from Lonza to K.F., and from MedImmune Cambridge to P.H. The University of Manchester/Melbourne collaboration scheme supported the travel costs of H.G., T.A.W., and F.S. The authors also thank Rehana Sung and Dr. Derren Heyes for their assistance with the HPLC and CD experiments. We are also grateful to Dr. Thomas Arnold from Diamond Light Source for help with the BAM imaging. Finally, we acknowledge the neutron beam time awarded by the ISIS Neutron Source (Experiments RB1920156: DOI 10.5286/ISIS.E.RB1920156, RB1820133: DOI 10.5286/ISIS. E. RB1820133, RB1820135: DOI 10.5286/ISIS.E.RB1820135 and RB1720227: DOI 10.5286/ISIS.E. RB1720227), and the Institut Laue-Langevin (DOI 10.5291/ILL-DATA.TEST-2894). We thank grant support from a Marie Curie Fellowship ITN grant (grant number 608184) under SNAL (small nano-objects for alteration of lipid bilayers) and a BBSRC LINK grant with AstraZeneca (BB/S018492/1).