title: Histatin 5 resistance of Candida glabrata can be reversed by insertion of Candida albicans polyamine transporter-encoding genes DUR3 and DUR31.
abstract: Candida albicans and Candida glabrata are predominant fungi associated with oral candidiasis. Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant. Since Hst 5 requires fungal binding to cell wall components prior to intracellular translocation, reduced Hst 5 binding to C. glabrata may be the reason for its insensitivity. C. glabrata has higher surface levels of β-1,3-glucans as compared with C. albicans; however these differences did not account for reduced Hst 5 uptake and killing in C. glabrata. Similarly, the biofilm matrix of C. glabrata contained significantly higher levels of β-1,3-glucans compared with C. albicans, but it did not reduce the percentage of Hst 5 positive fungal cells in the biofilm. Hst 5 enters C. albicans cell through polyamine transporters Dur3p and Dur31p that are uncharacterized in C. glabrata. C. glabrata strains expressing CaDur3 and CaDur31 had two-fold higher killing and uptake of Hst 5. Thus, neither C. glabrata cell surface or biofilm matrix β-1,3-glucan levels affected Hst 5 toxicity; rather the crucial rate limiting step is reduced uptake that can be overcome by expression of C. albicans Dur proteins in C. glabrata.
authors.affiliation: Department of Oral Biology, University at Buffalo, Buffalo, New York, USA.
authors.forename: Swetha
authors.initials: S
authors.lastname: Tati
authors.forename: Woong Sik
authors.initials: WS
authors.lastname: Jang
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Rohitashw
authors.initials: R
authors.lastname: Kumar
authors.forename: Sumant
authors.initials: S
authors.lastname: Puri
authors.forename: Mira
authors.initials: M
authors.lastname: Edgerton
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002176:Candida albicans / Q000235:genetics*; D041221:Candida glabrata / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005936:Glucans / Q000378:metabolism; D054808:Histatins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D016254:Mutagenesis, Insertional; D021381:Protein Transport / Q000235:genetics; D013095:Spermidine / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D005936:Glucans; C068075:HTN3 protein, human; D054808:Histatins; D013095:Spermidine