Avaliação da virulência e imunogenicidade da espécie emergente Sporothrix brasiliensis
Data
2015-03-12
Autores
Della Terra, Paula Portella 
Orientadores
Camargo, Zoilo Pires de
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A esporotricose é uma infecção fúngica crônica granulomatosa subcutânea e polimórfica que afeta homens e animais. O complexo Sporothrix schenckii que agrega os agentes etiológicos causadores desta micose é composto pelas espécies S. brasiliensis, S. schenckii sensu stricto (s. str.), S. globosa e S. luriei. Estes fungos apresentam dimorfismo térmico e alcançam o hospedeiro via inoculação traumática pelo contato com vegetais, solo e animais infectados, entre eles, felinos e tatus. Esta micose apresenta distribuição mundial, com focos endêmicos em países de clima tropical e subtropical. Nas últimas décadas, foram relatados surtos da doença no Brasil por S. brasiliensis intimamente relacionados à transmissão zoonótica por gatos infectados. Este estudo tem como principais objetivos, avaliar o perfil de virulência de isolados representativos de S. brasiliensis, utilizando S. schenckii s. str. e S. globosa como controles. Avaliou-se o perfil de secreção de proteínas/glicoproteínas e a imunogenicidade de tais moléculas. O estudo de patogenicidade foi conduzido através de infecção subcutânea em modelo murino com o intuito de mimetizar a principal rota de infecção. Desta forma, camundongos foram infectados por via subcutânea na pata esquerda com 5x106 leveduras de cada isolado de S. brasiliensis e controles. Os isolados de S. brasiliensis apresentaram diferentes perfis de virulência sendo classificados como pouco, médio e altamente virulento através da análise de carga fúngica presente nos órgãos, perda de peso, indução à morte dos animais infectados. A análise histopatológica revelou lesões teciduais principalmente quando isolados mais virulentos foram inoculados, confirmando a alta capacidade invasiva do S. brasiliensis. Os perfis proteicos dos isolados foram heterogênios. A maioria dos exoantígenos apresentaram proteínas/glicoproteínas de 30 e 35 kDa. Diferentes proteínas dos exoantígenos foram reconhecidas por IgG nos soros de camundongos infectados, sendo a molécula de 70 kDa a mais reconhecida. Os soros dos camundongos infectados com os isolados estudados reconheceram principalmente as moléculas de 100 kDa e 70 kDa presentes no extrato total do isolado Ss54 (S. brasiliensis) e Ss118 (S. schenckii). A caracterização da espécie de relevância epidemiológica no Brasil realizada neste estudo contribuiu para a melhor compreensão da patogênese da esporotricose.
Sporotrichosis is a polimorfic chronic granulomatous fungal infection that occurs in human and animals. Sporothrix schenckii complex that contain etiologic agents that causes this mycosis and is composed for species S. brasiliensis, S. schenckii sensu stricto (s. str.), S. globosa and S. luriei. This fungus presents thermal dimorphism and infects the host via traumatic inoculation by contact with plants, soil and animals, among them cats and armadillos. This mycosis has a worldwide distribution, with endemic areas in countries with subtropical and tropical weather. Over the last decades outbreaks this disease were reported in Brazil, mainly due to S. brasiliensis which were intimately related with zoonotic transmission by cats. The aims of this study was to evaluate the virulence profile of representative isolates of S. brasiliensis, using S. schenckii s. str. and S. globosa as controls. We evaluate the profile of secretion of protein/glycoprotein and the immunogenicity of these molecules. The pathogenicity study was conducted using a murine model of subcutaneous infection in order to simulate the major route of infection. Thus, mice were infected subcutaneously in the left paw with 5x106 of each isolate of S. brasiliensis and controls species. S. brasiliensis isolates showed different virulence profiles being classified as low, medium or high virulence based on the fungal burden in the organs evaluated, weight loss, and induction of death of infected animals. The histopathological analysis revealed tissue damage especially when most virulent isolates were inoculated, confirming the high invasiveness of S. brasiliensis. The protein profiles of isolates were heterogeneous. Most exoantigens present proteins/glycoproteins of 30- and 35-kDa. Different proteins of the exoantigens were recognized by IgG in the sera of infected mice, with a 70-kD molecule being frequently recognized. Sera from infected mice mainly recognized the molecules of 100-kDa and 70-kDa present in total extracts of Ss54 (S. brasiliensis) and SS118 (S. schenckii). The characterization of the species of major relevance in the epidemiological scenario in Brazil contributed to a better understanding of the pathogenesis of sporotrichosis.
Sporotrichosis is a polimorfic chronic granulomatous fungal infection that occurs in human and animals. Sporothrix schenckii complex that contain etiologic agents that causes this mycosis and is composed for species S. brasiliensis, S. schenckii sensu stricto (s. str.), S. globosa and S. luriei. This fungus presents thermal dimorphism and infects the host via traumatic inoculation by contact with plants, soil and animals, among them cats and armadillos. This mycosis has a worldwide distribution, with endemic areas in countries with subtropical and tropical weather. Over the last decades outbreaks this disease were reported in Brazil, mainly due to S. brasiliensis which were intimately related with zoonotic transmission by cats. The aims of this study was to evaluate the virulence profile of representative isolates of S. brasiliensis, using S. schenckii s. str. and S. globosa as controls. We evaluate the profile of secretion of protein/glycoprotein and the immunogenicity of these molecules. The pathogenicity study was conducted using a murine model of subcutaneous infection in order to simulate the major route of infection. Thus, mice were infected subcutaneously in the left paw with 5x106 of each isolate of S. brasiliensis and controls species. S. brasiliensis isolates showed different virulence profiles being classified as low, medium or high virulence based on the fungal burden in the organs evaluated, weight loss, and induction of death of infected animals. The histopathological analysis revealed tissue damage especially when most virulent isolates were inoculated, confirming the high invasiveness of S. brasiliensis. The protein profiles of isolates were heterogeneous. Most exoantigens present proteins/glycoproteins of 30- and 35-kDa. Different proteins of the exoantigens were recognized by IgG in the sera of infected mice, with a 70-kD molecule being frequently recognized. Sera from infected mice mainly recognized the molecules of 100-kDa and 70-kDa present in total extracts of Ss54 (S. brasiliensis) and SS118 (S. schenckii). The characterization of the species of major relevance in the epidemiological scenario in Brazil contributed to a better understanding of the pathogenesis of sporotrichosis.
Descrição
Citação
DELLA TERRA, Paula Portella. Avaliação da virulência e imunogenicidade da espécie emergente sporothrix brasiliensis. 2015. 119 f. Dissertação (Mestrado em Infectologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.