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Oral candidiasis can be presented in different ways due to the virulence factors of its etiology such as Candida albicansthat have developed an effective set of these factors that are able to improve its pathogenesis. The role of salivary immunological components in the development of candidiasis can provide insights for the development of new methodologies aiming to control this disease. The aim of this study was to evaluate the antifungal activity of two salivary components, histatin 5 and lactoferrin on C. albicansviability and virulence using a fluconazole resistant C. albicansclinical strain. Results showed that histatin 5 and lactoferrin decreased cell viability, and the cell surface hydrophobicity was increased by 18% in presence of 151 µg/mL of histatin 5 but was not altered by lactoferrin. It was observed the reduction of 69.3% in the expression of mannoproteins on C. albicanssurface in the presence of 151 µg/mL of histatin, but proteolytic activity of serine proteinases was not inhibited by any of the proteins. Histatin 5 altered cell ultrastructure predominantly in the cytoplasmic compartment. However, this peptide does not interfere with mitochondrial function neither in membrane permeability of the yeasts. The association index between C. albicansand epithelial cells was increased by 51% in presence of 151 µg/mL of histatin. Results suggest that histatin 5 and lactoferrin affects viability and virulence of C. albicansat physiological levels, and the maintenance of these levels may be essential in the prevention of oropharyngeal candidiasis. Exogenous administration of these proteins may become a therapeutic alternative for resistant strains of C. albicans, circumventing toxicity issues, considering their constitutive features.

Objectives: The aim of this study was to evaluate the ability of lapachones in disrupting the fungal multidrug resistance (MDR) phenotype, using a model of study which an azole-resistant Saccharomyces cerevisiaemutant strain that overexpresses the ATP-binding cassette (ABC) transporter Pdr5p. Methods: The evaluation of the antifungal activity of lapachones and their possible synergism with fluconazole against the mutant S. cerevisiaestrain was performed through broth microdilution and spot assays. Reactive oxygen species (ROS) and efflux pump activity were assessed by fluorometry. ATPase activity was evaluated by the Fiske and Subbarow method. The effect of β-lapachone on PDR5mRNA expression was assessed by RT-PCR. The release of hemoglobin was measured to evaluate the hemolytic activity of β-lapachone. Results: α-nor-Lapachone and β-lapachone inhibited S. cerevisiaegrowth at 100 μg/ml. Only β-lapachone enhanced the antifungal activity of fluconazole, and this combined action was inhibited by ascorbic acid. β-Lapachone induced the production of ROS, inhibited Pdr5p-mediated efflux, and impaired Pdr5p ATPase activity. Also, β-lapachone neither affected the expression of PDR5nor exerted hemolytic activity. Conclusions: Data obtained indicate that β-lapachone is able to inhibit the S. cerevisiaeefflux pump Pdr5p. Since this transporter is homologous to fungal ABC transporters, further studies employing clinical isolates that overexpress these proteins will be conducted to evaluate the effect of β-lapachone on pathogenic fungi.