ArticleThe FEBS journal2018
Engineering improved variants of the antifungal peptide histatin 5 with reduced susceptibility to Candida albicans secreted aspartic proteases and enhanced antimicrobial potency.
Article in The FEBS journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Antimicrobial peptides in the era of resistance: integrating AI-driven design, host-microbe interactions, and nanotechnological delivery.Frontiers in microbiology · 2026Review
- Optimizing Histatin 5: Effects of K13 and K17 Substitutions on Proteolytic Stability and Antifungal Activity.Computational and structural biotechnology journal · 2026Article
- Protective effect of histatin 5 and amphotericin B conjugated nanostructures in C. albicans challenged Swiss albino mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Exploring the Healing Powers of Histatins: From Oral Health to Therapeutics.International journal of molecular sciences · 2025Review
- Reducing Functional Domain of Histatin 5 Improves Antifungal Activity and Prevents Proteolytic Degradation.Microorganisms · 2025Article
- Therapeutic potential of mesenchymal stem cells for fungal infections: mechanisms, applications, and challenges.Frontiers in microbiology · 2025Review
- Role of amino acid substitutions on proteolytic stability of histatin 5 in the presence of secreted aspartyl proteases and salivary proteases.Protein science : a publication of the Protein Society · 2025Article
- Secreted Aspartic Proteinases: Key Factors inInternational journal of molecular sciences · 2024Review
- Activatable prodrug for controlled release of an antimicrobial peptide via the proteases overexpressed inTheranostics · 2024Article
- Antifungal activity of compounds fromHeliyon · 2023Article
- Strategies and opportunities for engineering antifungal peptides for therapeutic applications.Current opinion in biotechnology · 2023Review
- Quantifying the Antifungal Activity of Peptides Against Candida albicans.Journal of visualized experiments : JoVE · 2023Article
- Histatin 5 variant reduces Candida albicans biofilm viability and inhibits biofilm formation.Fungal genetics and biology : FG & B · 2021Article
- An orally available hypoglycaemic peptide taken up by caveolae transcytosis displays improved hypoglycaemic effects and body weight control in db/db mice.British journal of pharmacology · 2020Article
- Online capillary electrophoresis - mass spectrometry analysis of histatin-5 and its degradation products.The Analyst · 2020Article
- Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance.Microorganisms · 2020Review
- The Interactions between the Antimicrobial Peptide P-113 and LivingInternational journal of molecular sciences · 2020Article
- Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis.Protein science : a publication of the Protein Society · 2020Article
- Phage display as a tool for vaccine and immunotherapy development.Bioengineering & translational medicine · 2020Review
- Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
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