Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex.

AIMS: The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex. METHODS AND RESULTS: Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 µg ml(-1) to 21·6% after exposure to 64 µg ml(-1) of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy. CONCLUSIONS: Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis.

Antifungal susceptibility patterns of yeasts and filamentous fungi isolated from nail infection.

BACKGROUND: Onychomycosis is the nail infection caused by a wide spectrum of fungi species, including yeasts, dermatophytes and filamentous fungi non-dermatophytes (FFND). This fungal infection represents an important medical problem because it involves the patient's life quality. OBJECTIVE: The aim was to isolate and identify the fungal agents of onychomycosis, and to determine the in vitro susceptibility to antifungal agents. METHODS: During the period of March 2008 to March 2009, 114 patients clinically suspected of having onychomycosis were examined. Demographic data, mainly age and gender were obtained from each patient. The nail samples collected (136) were submitted to direct examination with potassium hydroxide 20% and grown on Sabouraud dextrose agar. The in vitro antifungal susceptibility testing was performed according to the method of broth microdilution, recommended by the Clinical Laboratory Standards Institute (CLSI). RESULTS: Onychomycosis was observed in 95 (83.3%) patients, including 16 men (16.8%) and 79 women (83.2%), with mean age of 48.1 years. Candida parapsilosis, Trichophyton rubrum and Fusarium spp were the fungi most frequently isolated. The most of the isolated yeasts showed susceptibility to antifungal agents studied. Among filamentous fungi, high MIC values to itraconazole were found for T. rubrum and T. mentagrophytes, while Fusarium spp showed decreased susceptibility to itraconazole and voriconazole. CONCLUSION: C. parapsilosis was the most common fungal species isolated from patients with onychomycosis. The different response obtained by in vitro susceptibility testing to drugs shows the importance of these methods to assist clinicians in choosing the best therapeutic option.

Epidemiological and mycological data of onychomycosis in Goiania, Brazil.

Onychomycosis defined as fungal infection of the nail represents more than 50% of all onychopathies. Epidemiological studies have shown that this mycosis is worldwide in occurrence, but with geographical variation in distribution. The direct microscopy and culture of the nail samples were performed to identify the causative agent. Out of 2273 patients with nail infection examined between January 2000 and December 2004 in Goiania, state of Goias, Brazil, diagnosis of onychomycosis was confirmed in 1282 cases, with dermatophytes and Candida species being the most common aetiological agents isolated. Dermatophyte onychomycosis was more common in toenails than in fingernails, while onychomycosis caused by yeast had a similar frequency in both toenails and fingernails. Among the species identified, Candida albicans was responsible for 492 cases (38.4%) of onychomycosis, Trichophyton rubrum was found in 327 cases (25.6%) and Trichophyton mentagrophytes in 258 cases (20.1%). Other fungi isolated from nail infections included Aspergillus sp., Trichosporon sp., Geotrichum sp. and Fusarium sp. In our study, yeast of the genus Candida were the dominant cause of onychomycosis in women and dermatophytes were the principal cause of this condition in men.

Antifungal activity of Ocimum gratissimum towards dermatophytes.

The development of more effective and less toxic antifungal agents is required for the treatment of dermatophytosis. Plants and their preparations have been used as medicines against infectious diseases. Extracts of Ocimum gratissimum leaves were investigated for in vitro antifungal activity, using agar dilution technique against dermatophytes. The extracts (hexane, chloroform fractions, the essential oil and eugenol) produced antifungal activities against Microsporum canis, M. gypseum, Trichophyton rubrum and T. mentagrophytes. Trichophyton rubrum, the most common aetiological agent of dermatophytosis in Goiânia, state of Goiás, Brazil, was also the most susceptible dermatophyte. The hexane fraction and eugenol were the most active. Hexane fraction inhibited the growth of 100% of dermatophytes at a concentration of 125 microg ml(-1), while eugenol inhibited the growth of 80% of dermatophytes at this same concentration. These results show that extracts of O. gratissimum are active in vitro against human pathogenic dermatophytes.