Curvelo Jose Alexandre da Rocha, Barreto Anna Lea Silva, Bayona-Pacheco Brayan Leonardo, de Moraes Daniel Clemente, Portela Maristela Barbosa, Ferreira-Pereira Antônio, Adade Camila Marques, Souto-Padrón Thaïs, Soares Rosangela Maria de Araújo
Divisão de Pesquisa clínica, Instituto Nacional do Câncer Marcelo Alencar, Rio de Janeiro, Brazil.
Grande Área Ciências Biológicas e da Saúde, Centro Universitário IBMR, Rio de Janeiro, Brazil.
Braz J Microbiol. 2024 Dec;55(4):3811-3825. doi: 10.1007/s42770-024-01517-5. Epub 2024 Sep 25.
Oral candidiasis can be presented in different ways due to the virulence factors of its etiology such as Candida albicans that 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. albicans viability and virulence using a fluconazole resistant C. albicans clinical 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. albicans surface 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. albicans and 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. albicans at 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.
由于其病因的毒力因素,如白色念珠菌,口腔念珠菌病可以以不同的方式呈现,白色念珠菌已经形成了一套有效的这些因素,能够改善其发病机制。唾液免疫成分在念珠菌病发展中的作用可为旨在控制这种疾病的新方法的开发提供见解。本研究的目的是使用对氟康唑耐药的白色念珠菌临床菌株,评估两种唾液成分,即组蛋白5和乳铁蛋白对白色念珠菌活力和毒力的抗真菌活性。结果表明,组蛋白5和乳铁蛋白降低了细胞活力,在151μg/mL组蛋白5存在下,细胞表面疏水性增加了18%,但乳铁蛋白未改变其疏水性。在151μg/mL组蛋白存在下,观察到白色念珠菌表面甘露糖蛋白表达降低了69.3%,但任何一种蛋白质均未抑制丝氨酸蛋白酶的蛋白水解活性。组蛋白5主要在细胞质区室改变细胞超微结构。然而,该肽既不干扰酵母的线粒体功能,也不干扰酵母的膜通透性。在151μg/mL组蛋白5存在下,白色念珠菌与上皮细胞之间的结合指数增加了51%。结果表明,组蛋白5和乳铁蛋白在生理水平上影响白色念珠菌的活力和毒力,维持这些水平可能对预防口咽念珠菌病至关重要。考虑到它们的组成特性,这些蛋白质的外源性给药可能成为白色念珠菌耐药菌株的一种治疗选择,规避毒性问题。