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Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms

Pfeil, M-P; Pyne, ALB; Losasso, V; Ravi, J; Lamarre, B; Faruqui, N; Alkassem, H; ... Ryadnov, MG; + view all (2018) Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms. Scientific Reports , 8 , Article 14926. 10.1038/s41598-018-33289-y. Green open access

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Abstract

The spread of antimicrobial resistance stimulates discovery strategies that place emphasis on mechanisms circumventing the drawbacks of traditional antibiotics and on agents that hit multiple targets. Host defense peptides (HDPs) are promising candidates in this regard. Here we demonstrate that a given HDP sequence intrinsically encodes for tuneable mechanisms of membrane disruption. Using an archetypal HDP (cecropin B) we show that subtle structural alterations convert antimicrobial mechanisms from native carpet-like scenarios to poration and non-porating membrane exfoliation. Such distinct mechanisms, studied using low- and high-resolution spectroscopy, nanoscale imaging and molecular dynamics simulations, all maintain strong antimicrobial effects, albeit with diminished activity against pathogens resistant to HDPs. The strategy offers an effective search paradigm for the sequence probing of discrete antimicrobial mechanisms within a single HDP.

Type: Article
Title: Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-018-33289-y
Publisher version: https://doi.org/10.1038/s41598-018-33289-y
Language: English
Additional information: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10060596
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