RESUMEN
Aim: This study evaluated the antifungal efficacy of gentian violet (GV) in an experimental vulvovaginal candidiasis (VVC) model. Materials & methods: In vitro susceptibility and cytotoxicity assays were performed to validate the antifungal potential and safety of GV. The antifungal efficacy was then evaluated in vivo through comparative analysis of the fungal burden following treatment with GV or nystatin, as well as assessment of the vaginal tissue by histology and electron microscopy. Results: GV demonstrated a safe antifungal profile against C. albicans, with a significant decrease in fungal burden and an improvement in the inflammatory process evaluated histologically. Conclusion: The results of this study motivate further assessment of GV as a promising alternative for VVC therapy.
Asunto(s)
Candidiasis Vulvovaginal , Femenino , Humanos , Ratones , Animales , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Violeta de Genciana/uso terapéutico , Candida albicans , Nistatina/farmacología , Nistatina/uso terapéuticoRESUMEN
Aim: To evaluate changes in virulence and pathogenicity approaches from Candida albicans after successive passages in a murine model of systemic candidiasis. Materials & methods: Phenotypic assays were performed using colonies recovered from animals infected serially, totalizing five passages. Results: A progressive infection was observed along the passages, with increased fungal burden and the presence of greater inflammatory areas in the histopathological findings. Recovered strains exhibited increased filamentation and biofilm abilities, along with modulation of phospholipase and proteinase activities. Conclusion: Repeated contact between yeast and host increased the expression of virulence factors. Furthermore, a correspondence between phenotypic profile and proteomic data obtained previously was observed.
Asunto(s)
Candida albicans/patogenicidad , Candidiasis/microbiología , Factores de Virulencia/metabolismo , Animales , Biopelículas/crecimiento & desarrollo , Candida albicans/crecimiento & desarrollo , Candida albicans/metabolismo , Recuento de Colonia Microbiana , Citocinas/metabolismo , Modelos Animales de Enfermedad , Riñón/metabolismo , Riñón/microbiología , Riñón/patología , Ratones , Péptido Hidrolasas/metabolismo , Fosfolipasas/metabolismoRESUMEN
Aim: A structural model of chorismate synthase (CS) from the pathogenic fungus Candida albicans was used for virtual screening simulations. Methods: Docking, molecular dynamics, cell growth inhibition and protein binding assays were used for search and validation. Results: Two molecules termed CS8 and CaCS02 were identified. Further studies of the minimal inhibitory concentration demonstrated fungicidal activity against Paracoccidioides brasiliensis with a minimal inhibitory concentration and minimal fungicidal concentration of 512 and 32 µg·ml-1 for CS8 and CaCS02, respectively. In addition, CaCS02 showed a strong synergistic effect in combination with amphotericin B without cytotoxic effects. In vitro studies using recombinant CS from P. brasiliensis showed IC50 of 29 µM for CaCS02 supporting our interpretation that inhibition of CS causes the observed fungicidal activity.
Asunto(s)
Antifúngicos/farmacología , Proteínas Fúngicas/antagonistas & inhibidores , Paracoccidioides/efectos de los fármacos , Liasas de Fósforo-Oxígeno/antagonistas & inhibidores , Secuencia de Aminoácidos , Anfotericina B/farmacología , Animales , Antifúngicos/química , Antifúngicos/metabolismo , Candida albicans/enzimología , Chlorocebus aethiops , Sinergismo Farmacológico , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Células HeLa , Humanos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Paracoccidioides/enzimología , Liasas de Fósforo-Oxígeno/química , Liasas de Fósforo-Oxígeno/metabolismo , Unión Proteica , Células VeroRESUMEN
Aim: To evaluate the efficacy of photodynamic inactivation (PDI) mediated by hypericin encapsulated in P-123 copolymeric micelles (P123-Hyp) alone and in combination with fluconazole (FLU) against planktonic cells and biofilm formation of Candida species Materials & methods: PDI was performed using P123-Hyp and an LED device with irradiance of 3.0 mW/cm2 . Results: Most of isolates (70%) were completely inhibited with concentrations up to 2.0 µmol/l of HYP and light fluence of 16.2 J/cm2. FLU-resistant strains had synergic effect with P123-HYP-PDI and FLU. The biofilm formation was inhibited in all species, in additional the changes in Candida morphology observed by scanning electron microscopy. Conclusion: P123-Hyp-PDI is a promising option to treat fungal infections and medical devices to prevent biofilm formation and fungal spread.