RESUMO
Sporothrix schenckii is a pathogenic dimorphic fungus with a global distribution. It grows in a multicellular hyphal form at 25ËC and a unicellular yeast form at 37ËC. The morphological switch from mold to yeast form is obligatory for establishing pathogenicity in S. schenckii. Twocomponent signaling systems are utilized by eukaryotes to sense and respond to external environmental changes. DRK1is a hybrid histidine kinase, which functions as a global regulator of dimorphism and virulence in Blastomyces dermatitidis and Histoplasma capsulatum. An intracellular soluble hybrid histidine kinase, homologous to DRK1 in B. dermatitidis, has previously been identified in S. schenckii and designated as SsDRK1. In the present study, the function of SsDRK1 was investigated using double stranded RNA interference mediated by Agrobacterium tumefaciens. SsDRK1 was demonstrated to be required for normal asexual development, yeastphase cell formation, cell wall composition and integrity, melanin synthesis, transcription of the morphogenesisassociated gene Ste20 that is involved in the high osmolarity glycerol/mitogenactivated protein kinase pathway, and pathogenicity of S. schenckii in a murine model of cutaneous infection. Further investigations into the signals SsDRK1 responds to, and the interactions of upstream transmembrane hybrid histidine kinases with SsDRK1, are required to uncover novel targets for antifungal therapies.
Assuntos
Histidina Quinase/genética , Sporothrix/patogenicidade , Esporotricose/genética , Agrobacterium tumefaciens , Blastomyces/enzimologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Histoplasma/enzimologia , Humanos , Hifas/enzimologia , Hifas/genética , Hifas/patogenicidade , MAP Quinase Quinase Quinases/genética , Morfogênese/genética , Concentração Osmolar , RNA de Cadeia Dupla/genética , Proteínas de Saccharomyces cerevisiae/genética , Sporothrix/enzimologia , Sporothrix/genética , Esporotricose/enzimologia , Esporotricose/microbiologiaAssuntos
Quitina Sintase/metabolismo , Sporothrix/enzimologia , Esporotricose/enzimologia , Idoso , Biópsia , Pré-Escolar , Quitina Sintase/genética , DNA Fúngico/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Esporotricose/genética , Esporotricose/patologiaRESUMO
Granuloma formation is a common response in the skin infection of sporotrichosis. The involvement of interferon-gamma (IFN-gamma) and inducible nitric oxide synthase (iNOS) in the granuloma formation of sporotrichosis is less known. The aim of this study was to describe by immunohistochemistry the exact tissue distribution of IFN-gamma-positive cells and iNOS-positive cells in the granuloma of skin lesions from patients with sporotrichosis. Formalin-fixed paraffin-embedded skin biopsy sections from five patients were stained by immunohistochemical methods. Mixture of CD4-positive T cells and CD8-positive T cells were present in and around the granulomatous lesions. IFN-gamma-positive cells, like mononuclear lymphoid cells, were detected in the periphery of the granulomas in all samples. The pattern of IFN-gamma staining appeared to be a combination of intracellular staining in mononuclear lymphoid cells and extracellular deposition in the surrounding tissue. The majority of the epitheloid cells and multinucleated giant cells within the granuloma were identified by immunostaining for CD68. In contrast, no expression of immunoreactive iNOS was observed in those cells in all samples. These findings indicate that granulomas of sporotrichosis are coupled with Th1 response.