• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2018
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2018
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Engineering improved variants of the antifungal peptide histatin 5 with reduced susceptibility to Candida albicans secreted aspartic proteases and enhanced antimicrobial potency

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Ikonomova, S.P.
    Moghaddam-Taaheri, P.
    Jabra-Rizk, M.A.
    Date
    2018
    Journal
    FEBS Journal
    Publisher
    Blackwell Publishing Ltd
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1111/febs.14327
    Abstract
    Candida albicans is an opportunistic fungal pathogen and a commensal organism that commonly colonizes mucosal surfaces, including those inside the human mouth. To help control C. albicans, human saliva contains the antifungal peptide histatin 5 (Hst-5), which has strong antifungal activity against C. albicans. However, the pathogen produces secreted aspartic proteases (Saps) that cleave Hst-5 at lysine residues and eliminate its antifungal properties. We designed variants of Hst-5 with its lysine residues substituted with arginine or leucine to evaluate the effect on proteolysis by Saps. We found site-, residue-, and Sap-dependent effects from single amino acid substitutions. The K17R and K17L modifications led to dramatic results, with over 77% and 100% intact peptide remaining after incubation with Sap9 and Sap2, respectively, compared to 47% and 61% of Hst-5. This decrease in proteolysis was accompanied by a reduction in cleavage on the C-terminal side of K17, suggesting the Saps prefer lysine at K17 for cleavage. Incubation with C. albicans cells and culture supernatant corroborated the results with purified Saps and highlighted their biological relevance. The modifications to Hst-5 do not diminish the antifungal activity of Hst-5, and, in fact, the K17R, K17L, and K11R peptides retained significantly more antifungal activity after treatment with Saps than Hst-5. Our results indicate that single amino acid modifications drastically impact both proteolysis at the modification sites and the overall level of proteolysis of the peptide, demonstrating the potential of designing peptides for resistance to proteolysis as a means for improving therapeutic efficacy. Copyright 2017 Federation of European Biochemical Societies
    Sponsors
    We thank Bernhard Hube for providing the purified Saps. This work was supported by a National Institutes of Health training grant in Host-Pathogen Interactions (T32AI089621B) and a University of Maryland Cross-Campus Seed Grant.
    Keyword
    antimicrobial peptides
    Candida albicans
    histatin-5
    proteolysis
    secreted aspartic proteases
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85036546240&doi=10.1111%2ffebs.14327&partnerID=40&md5=217b25bc940f7eda8a1400e6c5c538c1; http://hdl.handle.net/10713/9110
    ae974a485f413a2113503eed53cd6c53
    10.1111/febs.14327
    Scopus Count
    Collections
    UMB Open Access Articles 2018

    entitlement

    Related articles

    • Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis.
    • Authors: Ikonomova SP, Moghaddam-Taaheri P, Wang Y, Doolin MT, Stroka KM, Hube B, Karlsson AJ
    • Issue date: 2020 Feb
    • Histatin 5 variant reduces Candida albicans biofilm viability and inhibits biofilm formation.
    • Authors: Moghaddam-Taaheri P, Leissa JA, Eppler HB, Jewell CM, Karlsson AJ
    • Issue date: 2021 Apr
    • The action of ten secreted aspartic proteases of pathogenic yeast Candida albicans on major human salivary antimicrobial peptide, histatin 5.
    • Authors: Bochenska O, Rapala-Kozik M, Wolak N, Aoki W, Ueda M, Kozik A
    • Issue date: 2016
    • Evaluation of the Antifungal and Wound-Healing Properties of a Novel Peptide-Based Bioadhesive Hydrogel Formulation.
    • Authors: Sultan AS, Vila T, Hefni E, Karlsson AJ, Jabra-Rizk MA
    • Issue date: 2019 Oct
    • Inactivation of the antifungal and immunomodulatory properties of human cathelicidin LL-37 by aspartic proteases produced by the pathogenic yeast Candida albicans.
    • Authors: Rapala-Kozik M, Bochenska O, Zawrotniak M, Wolak N, Trebacz G, Gogol M, Ostrowska D, Aoki W, Ueda M, Kozik A
    • Issue date: 2015 Jun
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.