ArticleThe Journal of biological chemistry2011
Histatin 5 uptake by Candida albicans utilizes polyamine transporters Dur3 and Dur31 proteins.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- Article
- Exploring the Healing Powers of Histatins: From Oral Health to Therapeutics.International journal of molecular sciences · 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
- A synthetic peptide mimic kills Candida albicans and synergistically prevents infection.Nature communications · 2024Article
- Combating fungal phytopathogens with human salivary antimicrobial peptide histatin 5 through a multi-target mechanism.World journal of microbiology & biotechnology · 2023Article
- Zinc Binding Inhibits Cellular Uptake and Antifungal Activity of Histatin-5 inACS infectious diseases · 2022Article
- Antimicrobial Peptides with Anti-International journal of molecular sciences · 2022Review
- Salivary Histatin 5 Level in Women with Vaginal Candidiasis.International journal of clinical practice · 2022Article
- Envisaging Antifungal Potential of Histatin 5: A Physiological Salivary Peptide.Journal of fungi (Basel, Switzerland) · 2021Review
- A Novel Role for Histatin 5 in Combination with Zinc to Promote Commensalism inPathogens (Basel, Switzerland) · 2021Article
- Mangiferin enhances the antifungal activities of caspofungin by destroying polyamine accumulation.Virulence · 2021Article
- Role of CgTpo4 in Polyamine and Antimicrobial Peptide Resistance: Determining Virulence inInternational journal of molecular sciences · 2021Article
- Membrane-Interacting Antifungal Peptides.Frontiers in cell and developmental biology · 2021Review
- Effect of Disulfide Cyclization of Ultrashort Cationic Lipopeptides on Antimicrobial Activity and Cytotoxicity.International journal of molecular sciences · 2020Article
- Zinc Binding by Histatin 5 Promotes Fungicidal Membrane Disruption inJournal of fungi (Basel, Switzerland) · 2020Article
- Chemokine CCL28 Is a Potent Therapeutic Agent for Oropharyngeal Candidiasis.Antimicrobial agents and chemotherapy · 2020Article
- Antifungal Peptides as Therapeutic Agents.Frontiers in cellular and infection microbiology · 2020Review
- Candida albicansmBio · 2019Article
- Methodologies forMicrobial cell (Graz, Austria) · 2018Review
- TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida.PLoS genetics · 2018Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Histatin 5 (Hst 5) is a salivary gland-secreted cationic peptide with potent fungicidal activity against Candida albicans. Hst 5 kills fungal cells following intracellular translocation, although its selective transport mechanism is unknown. C. albicans cells grown in the presence of polyamines were resistant to Hst 5 due to reduced intracellular uptake, suggesting that this cationic peptide may enter candidal cells through native yeast polyamine transporters. Based upon homology to known Saccharomyces cerevisiae polyamine permeases, we identified six C. albicans Dur polyamine transporter family members and propose a new nomenclature. Gene deletion mutants were constructed for C. albicans polyamine transporters Dur3, Dur31, Dur33, Dur34, and were tested for Hst 5 sensitivity and uptake of spermidine. We found spermidine uptake and Hst 5 mediated killing were decreased significantly in Δdur3, Δdur31, and Δdur3/Δdur31 strains; whereas a DUR3 overexpression strain increased Hst 5 sensitivity and higher spermidine uptake. Treatment of cells with a spermidine synthase inhibitor increased spermidine uptake and Hst 5 killing, whereas protonophores and cold treatment reduced spermidine uptake. Inhibition assays showed that Hst 5 is a competitive analog of spermidine for uptake into C. albicans cells, and that Hst 5 Ki values were increased by 80-fold in Δdur3/Δdur31 cells. Thus, Dur3p and Dur31p are preferential spermidine transporters used by Hst 5 for its entry into candidal cells. Understanding of polyamine transporter-mediated internalization of Hst 5 provides new insights into the uptake mechanism for C. albicans toxicity, and further suggests design for targeted fungal therapeutic agents.
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