Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives

ABSTRACT The rise of multidrug-resistant pathogens has awakened interest in new drug candidates such as antimicrobial peptides and their derivatives. Recent work suggests that some antimicrobial peptides have the ability to self-assemble into ordered amyloid-like nanostructures which facilitate thei...

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Autores principales:	Lee Schnaider, Alexander Rosenberg, Topaz Kreiser, Sofiya Kolusheva, Ehud Gazit, Judith Berman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	antimicrobial peptides histatins membrane interactions self-assembly Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8f4f1944f4e84afd981eb6ebf88e79c1
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spelling	oai:doaj.org-article:8f4f1944f4e84afd981eb6ebf88e79c12021-11-15T15:29:16ZPeptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives10.1128/mSphere.00021-202379-5042https://doaj.org/article/8f4f1944f4e84afd981eb6ebf88e79c12020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00021-20https://doaj.org/toc/2379-5042ABSTRACT The rise of multidrug-resistant pathogens has awakened interest in new drug candidates such as antimicrobial peptides and their derivatives. Recent work suggests that some antimicrobial peptides have the ability to self-assemble into ordered amyloid-like nanostructures which facilitate their antibacterial activity. Here, we evaluate a histatin-based antimicrobial peptide, and its self-assembling derivative, in the interplay between self-assembly, membrane interactions, and antibacterial and antifungal activities. We demonstrate substantial membrane targeting by both peptides, as well as mechanistic insights into this mode of action, which correlates to their antifungal activity and is not affected by their self-assembling state. The ability to self-assemble does, however, significantly affect peptide antibacterial activity against both Gram-negative and Gram-positive bacteria. These results are surprising and hint at important distinctions between antifungal and antibacterial peptide activities in prokaryotes and eukaryotic microbes. IMPORTANCE Antimicrobial peptides are important modulators of host defense against bacterial, fungal, and viral pathogens in humans and other multicellular organisms. Two converging paradigms point to a link between antimicrobial peptides that self-assemble into amyloid-like nanoassemblies and classical amyloidogenic peptides that often have potent broad-spectrum antimicrobial activity, suggesting that antimicrobial and amyloidogenic peptides may represent two sides of the same coin. Here, we asked if the ability of an antifungal peptide to self-assemble affects its antifungal or antibacterial activity. We found that modifications of classical antifungal peptide derivative allowed it to self-assemble and did not alter its antifungal activity, and yet self-assembly substantially increased the antibacterial activity of the peptide. These results support the idea that peptide self-assembly can enhance antibacterial activities and emphasize a distinction between the action of antifungal peptides and that of antibacterial peptides. Accordingly, we suggest that the possible generality of this distinction should be widely tested.Lee SchnaiderAlexander RosenbergTopaz KreiserSofiya KolushevaEhud GazitJudith BermanAmerican Society for Microbiologyarticleantimicrobial peptideshistatinsmembrane interactionsself-assemblyMicrobiologyQR1-502ENmSphere, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial peptides histatins membrane interactions self-assembly Microbiology QR1-502
spellingShingle	antimicrobial peptides histatins membrane interactions self-assembly Microbiology QR1-502 Lee Schnaider Alexander Rosenberg Topaz Kreiser Sofiya Kolusheva Ehud Gazit Judith Berman Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives
description	ABSTRACT The rise of multidrug-resistant pathogens has awakened interest in new drug candidates such as antimicrobial peptides and their derivatives. Recent work suggests that some antimicrobial peptides have the ability to self-assemble into ordered amyloid-like nanostructures which facilitate their antibacterial activity. Here, we evaluate a histatin-based antimicrobial peptide, and its self-assembling derivative, in the interplay between self-assembly, membrane interactions, and antibacterial and antifungal activities. We demonstrate substantial membrane targeting by both peptides, as well as mechanistic insights into this mode of action, which correlates to their antifungal activity and is not affected by their self-assembling state. The ability to self-assemble does, however, significantly affect peptide antibacterial activity against both Gram-negative and Gram-positive bacteria. These results are surprising and hint at important distinctions between antifungal and antibacterial peptide activities in prokaryotes and eukaryotic microbes. IMPORTANCE Antimicrobial peptides are important modulators of host defense against bacterial, fungal, and viral pathogens in humans and other multicellular organisms. Two converging paradigms point to a link between antimicrobial peptides that self-assemble into amyloid-like nanoassemblies and classical amyloidogenic peptides that often have potent broad-spectrum antimicrobial activity, suggesting that antimicrobial and amyloidogenic peptides may represent two sides of the same coin. Here, we asked if the ability of an antifungal peptide to self-assemble affects its antifungal or antibacterial activity. We found that modifications of classical antifungal peptide derivative allowed it to self-assemble and did not alter its antifungal activity, and yet self-assembly substantially increased the antibacterial activity of the peptide. These results support the idea that peptide self-assembly can enhance antibacterial activities and emphasize a distinction between the action of antifungal peptides and that of antibacterial peptides. Accordingly, we suggest that the possible generality of this distinction should be widely tested.
format	article
author	Lee Schnaider Alexander Rosenberg Topaz Kreiser Sofiya Kolusheva Ehud Gazit Judith Berman
author_facet	Lee Schnaider Alexander Rosenberg Topaz Kreiser Sofiya Kolusheva Ehud Gazit Judith Berman
author_sort	Lee Schnaider
title	Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives
title_short	Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives
title_full	Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives
title_fullStr	Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives
title_full_unstemmed	Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives
title_sort	peptide self-assembly is linked to antibacterial, but not antifungal, activity of histatin 5 derivatives
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/8f4f1944f4e84afd981eb6ebf88e79c1
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Peptide Self-Assembly Is Linked to Antibacterial, but Not Antifungal, Activity of Histatin 5 Derivatives

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