5-Aminolevulinic acid-mediated photodynamic therapy has effective antifungal activity against Sporothrix globosa in vitro.

BACKGROUND: An alternative therapy for sporotrichosis is necessary to reduce the treatment time and raise clinical efficacy. The 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a promising platform with which to treat mycoses. However, despite the worldwide prevalence of Sporothrix globosa, a causative agent of sporotrichosis, the effect of ALA-PDT on this pathogen has not been validated. OBJECTIVES: The aim of this study was to evaluate the effect of ALA-PDT on S globosa and the protection of melanin through an in vitro study. The mechanisms involved were also investigated. METHODS: To estimate the survival rate of S globosa treated with ALA-PDT and the protection offered by melanin, the conidia and yeast cells of wild-type S globosa (Mel+), other clinical strains, tricyclazole-treated Mel+ and an albino mutant strain (Mel-) were incubated with and without ALA or irradiation. Reactive oxygen species generation by Mel+ conidia induced by ALA-PDT was assayed. SEM and TEM were conducted to obverse ultrastructural changes in the conidia. A comet assay was performed to evaluate DNA damage. RESULTS: The survival rate of S globosa conidia and yeast cells significantly decreased following incubation with 1.19M ALA and 162 J/cm2 irradiation in vitro. Melanin was not only capable of protecting the conidia against ALA-PDT, but also against ALA or irradiation alone. After induction by ALA-PDT, alterations in reactive oxygen species generation, DNA damage and ultrastructural changes were observed. CONCLUSIONS: ALA-PDT inhibits the survival of S globosa conidia in vitro and therefore has potential for the treatment of sporotrichosis.

Antifungal curcumin promotes chitin accumulation associated with decreased virulence of Sporothrix schenckii.

Curcumin, a yellow polyphenol compound, is known to possess antifungal activity for a range of pathogenic fungi. However, the fungicidal mechanism of curcumin (CUR) has not been identified. We have occasionally found that chitin redistributes to the cell wall outer layer of Sporothrix schenckii (S. schenckii) upon sublethal CUR treatment. Whether CUR can affect chitin synthesis via the protein kinase C (PKC) signaling pathway has not been investigated. This study describes a direct fungicidal activity of CUR against S. schenckii demonstrated by the results of a checkerboard microdilution assay and, for the first time, a synergistic effect of CUR with terbinafine (TRB). Furthermore, the results of real-time PCR showed that sublethal CUR upregulated the transcription of PKC, chitin synthase1 (CHS1), and chitin synthase3 (CHS3) in S. schenckii. The fluorescence staining results using wheat germ agglutinin-fluorescein isothiocyanate (WGA-FITC) and calcofluor white (CFW) consistently showed that chitin exposure and total chitin content were increased on the conidial cell wall of S. schenckii by sublethal CUR treatment. A histopathological analysis of mice infected with CUR-treated conidia showed dampened inflammation in the local lesion and a reduced fungal burden. The ELISA results showed proinflammatory cytokine secretion at an early stage from macrophages stimulated by the CUR-treated conidia. The present data led to the conclusion that CUR is a potential antifungal agent and that its fungicidal mechanism may involve chitin accumulation on the cell wall of S. schenckii, which is associated with decreased virulence in infected mice.

In Vitro and In Vivo Efficacy of Amphotericin B Combined with Posaconazole against Experimental Disseminated Sporotrichosis.

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.

Comunicación de tres casos de esporotricosis en San Luis: una micosis de diagnóstico infrecuente en esta zona geográfica / Sporotrichosis in the province of San Luis: three cases presentation of an infrequent mycosis in our area

Presentamos a tres pacientes afectados de esporotricosis linfangítico-nodular, con las características comunes en lo concerniente a la clínica y el laboratorio. Lo distintivo estaría que nuestra área geográfica es naturalmente seca y, durante muchos meses del año, fría, es decir, una zona no apta para el desarrollo del hongo Sporothrix schenckil. Uno de nuestros pacientes se infectó, aparentemente, debido a una herida punzante con una astilla de material plástico. Exhortamos a los clínicos y dermatólogos de nuestra región a pensar en la esporotricosis como diagnóstico diferencial etiológico de todas las úlceras y abscesos "fríos" que no curen con los tratamientos habituales y por lo tanto su evolución crónica (AU)

Comunicación de tres casos de esporotricosis en San Luis: una micosis de diagnóstico infrecuente en esta zona geográfica / Sporotrichosis in the province of San Luis: three cases presentation of an infrequent mycosis in our area

Presentamos a tres pacientes afectados de esporotricosis linfangítico-nodular, con las características comunes en lo concerniente a la clínica y el laboratorio. Lo distintivo estaría que nuestra área geográfica es naturalmente seca y, durante muchos meses del año, fría, es decir, una zona no apta para el desarrollo del hongo Sporothrix schenckil. Uno de nuestros pacientes se infectó, aparentemente, debido a una herida punzante con una astilla de material plástico. Exhortamos a los clínicos y dermatólogos de nuestra región a pensar en la esporotricosis como diagnóstico diferencial etiológico de todas las úlceras y abscesos "fríos" que no curen con los tratamientos habituales y por lo tanto su evolución crónica