ArticleAntimicrobial agents and chemotherapy2013
Candida albicans flu1-mediated efflux of salivary histatin 5 reduces its cytosolic concentration and fungicidal activity.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- In Vivo Evaluation of Efficacy and Toxicity of Bioinspired Peptides With Antimicrobial Properties Against Fungal Infection inInternational journal of microbiology · 2026Article
- Reprogramming inInternational journal of molecular sciences · 2023Article
- Salicylic acid treatment and overexpression of a novel polyamine transporter gene for astaxanthin production inFrontiers in bioengineering and biotechnology · 2023Article
- Genomic landscape of the DHA1 family in Candida auris and mapping substrate repertoire of CauMdr1.Applied microbiology and biotechnology · 2022Article
- Genomic Data Mining Reveals Abundant Uncharacterized Transporters inJournal of fungi (Basel, Switzerland) · 2022Article
- Natural Variation and the Role of ZnMicroorganisms · 2022Article
- Salivary Histatin 5 Level in Women with Vaginal Candidiasis.International journal of clinical practice · 2022Article
- 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
- Mrr1 regulation of methylglyoxal catabolism and methylglyoxal-induced fluconazole resistance in Candida lusitaniae.Molecular microbiology · 2021Article
- Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance.Microorganisms · 2020Review
- Sho1p Connects Glycolysis to Ras1-cAMP Signaling and Is Required for Microcolony Formation in Candida albicans.mSphere · 2020Article
- Review
- "Tissue barriers · 2019Review
- Host-Pathogen Interactions Mediated by MDR Transporters in Fungi: As Pleiotropic as it Gets!Genes · 2018Review
- Functions ofPeerJ · 2018Article
- Fungal Strategies to Evade the Host Immune Recognition.Journal of fungi (Basel, Switzerland) · 2017Review
- An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses.PLoS pathogens · 2017Article
- Oropharyngeal Candidiasis: Fungal Invasion and Epithelial Cell Responses.PLoS pathogens · 2017Review
- Human Salivary Protein Histatin 5 Has Potent Bactericidal Activity against ESKAPE Pathogens.Frontiers in cellular and infection microbiology · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Histatin 5 (Hst 5) is a salivary human antimicrobial peptide that is toxic to the opportunistic yeast Candida albicans. Fungicidal activity of Hst 5 requires intracellular translocation and accumulation to a threshold concentration for it to disrupt cellular processes. Previously, we observed that total cytosolic levels of Hst 5 were gradually reduced from intact cells, suggesting that C. albicans possesses a transport mechanism for efflux of Hst 5. Since we identified C. albicans polyamine transporters responsible for Hst 5 uptake, we hypothesized that one or more polyamine efflux transporters may be involved in the efflux of Hst 5. C. albicans FLU1 and TPO2 were found to be the closest homologs of Saccharomyces cerevisiae TPO1, which encodes a major spermidine efflux transporter, indicating that the products of these two genes may be involved in efflux of Hst 5. We found that flu1Δ/Δ cells, but not tpo2Δ/Δ cells, had significant reductions in their rates of Hst 5 efflux and had significantly higher cytoplasmic Hst 5 and Hst 5 susceptibilities than did the wild type. We also found that flu1Δ/Δ cells had reduced biofilm formation compared to wild-type cells in the presence of Hst 5. Transcriptional levels of FLU1 were not altered over the course of treatment with Hst 5; therefore, Hst 5 is not likely to induce FLU1 gene overexpression as a potential mechanism of resistance. Thus, Flu1, but not Tpo2, mediates efflux of Hst 5 and is responsible for reduction of its toxicity in C. albicans.
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