ABSTRACT Sporothrix schenckii is a dimorphic fungus and the etiologic agent of human and animal sporotrichosis. This particular mycosis is endemic in South America and affects cutaneous and subcutaneous tissues. There are several clinical manifestations related according to both, the immune state of the host and intrinsic virulence factors of the pathogen. By 2007, molecular studies demonstrated that this specie comprehends a complex of cryptic species. Currently, in Brazil, the two most frequent species of the Sporothrix spp. complex found in the clinical isolates from patients with sporotrichosis are S. schenckii and S. brasiliensis. In Rio de Janeiro State, the most prevalent species is S. brasiliensis, and up to 2012, around 3000 cases in human and 4000 in cats were registered. The transmission occurs by traumatic implantation of the pathogen, which seem to use a paracellular route to disseminate, by adhering to the native subendothelial matrix (basal lamina). However, the molecules involved in the colonization and invasion processes are still unkown for S. schenckii and S. brasiliensis. The main aim of this work was to analyze the virulence profile of several strains of both species using three distinct models. The first one, an in vivo model of subcutaneous sporotrichosis, was used to analyze the extend of lesions and the dissemination pattern of the strains. The other two in vitro models, were used to analyze the adherence of the strains to the models: native subendothelial matrix (basal lamina) and artificial human dermis. To accomplish these experiments, eight strains were selected: two of S. schenckii and six of S. brasiliensis. The results showed that in the subcutaneous murine sporotrichosis model, the S. brasiliensis strains are overall more virulent when compared to S. schenckii. In contrast, the S. schenckii strains presented higher adherence to the extracellular matrix and to the artificial human dermis. Interestingly, the highest and the lowest virulent strains tested in this study belong to the S. brasiliensis species. Because of the great variability within the isolates of this species more studies are needed in order to correlate the virulence patterns and the adhesion capacity with the infective species within the Sporothrix complex. Interaction between Sporothrix schenckii complex isolates with dermal human model and native subendothelial matrix

Autor: Sanches, Glenda de Figueiredo
Přispěvatelé: Bezerra, Leila Maria Lopes, Costa, Rosane Orofino, Pacheco, Tânia Maria Valente, Almeida, Sandro Rogério de
Jazyk: portugalština
Rok vydání: 2013
Předmět:
Zdroj: Biblioteca Digital de Teses e Dissertações da UERJ
Universidade do Estado do Rio de Janeiro (UERJ)
instacron:UERJ
Popis: Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:58:38Z No. of bitstreams: 1 Glenda de Figueiredo Sanches Dissertacao completa.pdf: 3246822 bytes, checksum: 6bdd3d944373f825796ad9112cc2ae90 (MD5) Made available in DSpace on 2021-01-06T20:58:38Z (GMT). No. of bitstreams: 1 Glenda de Figueiredo Sanches Dissertacao completa.pdf: 3246822 bytes, checksum: 6bdd3d944373f825796ad9112cc2ae90 (MD5) Previous issue date: 2013-03-21 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Sporothrix schenckii is a dimorphic fungus and the etiologic agent of human and animal sporotrichosis. This particular mycosis is endemic in South America and affects cutaneous and subcutaneous tissues. There are several clinical manifestations related according to both, the immune state of the host and intrinsic virulence factors of the pathogen. By 2007, molecular studies demonstrated that this specie comprehends a complex of cryptic species. Currently, in Brazil, the two most frequent species of the Sporothrix spp. complex found in the clinical isolates from patients with sporotrichosis are S. schenckii and S. brasiliensis. In Rio de Janeiro State, the most prevalent species is S. brasiliensis, and up to 2012, around 3000 cases in human and 4000 in cats were registered. The transmission occurs by traumatic implantation of the pathogen, which seem to use a paracellular route to disseminate, by adhering to the native subendothelial matrix (basal lamina). However, the molecules involved in the colonization and invasion processes are still unkown for S. schenckii and S. brasiliensis. The main aim of this work was to analyze the virulence profile of several strains of both species using three distinct models. The first one, an in vivo model of subcutaneous sporotrichosis, was used to analyze the extend of lesions and the dissemination pattern of the strains. The other two in vitro models, were used to analyze the adherence of the strains to the models: native subendothelial matrix (basal lamina) and artificial human dermis. To accomplish these experiments, eight strains were selected: two of S. schenckii and six of S. brasiliensis. The results showed that in the subcutaneous murine sporotrichosis model, the S. brasiliensis strains are overall more virulent when compared to S. schenckii. In contrast, the S. schenckii strains presented higher adherence to the extracellular matrix and to the artificial human dermis. Interestingly, the highest and the lowest virulent strains tested in this study belong to the S. brasiliensis species. Because of the great variability within the isolates of this species more studies are needed in order to correlate the virulence patterns and the adhesion capacity with the infective species within the Sporothrix complex. O Sporothrix schenckii é um fugo dimórfico e agente etiológico da esporotricose humana e animal. Esta micose é endêmica na América do Sul e, envolve o tecido cutâneo e subcutâneo. Diferentes manifestações clínicas estão relacionadas com o estado imune do hospedeiro e fatores intrínsecos de virulência do patógeno. Desde 2007, estudos moleculares demonstraram que esta espécie, compreende um complexo de espécies crípticas. Atualmente, no Brasil, as duas espécies circulantes de maior importância são S. schenckii e S. brasiliensis. No Estado do Rio de Janeiro, a espécie mais prevalente é S. brasiliensis, onde até 2012 foram registrados cerca de 3000 casos de esporotricose humana e 4000 casos de esporotricose felina. Esta micose se dá pela implantação traumática do patógeno, que através de rota paracelular, adere à matriz subendotelial nativa (lâmina basal), iniciando a disseminação por via hematogênica. Porém, as moléculas envolvidas neste processo de colonização e invasão expressas por ambas as espécies ainda são pouco conhecidas. O principal objetivo deste trabalho foi analisar o perfil de virulência de isolados das espécies, S. schenckii e S. brasiliensis, através da comparação em três modelos distintos. O primeiro modelo utilizado, in vivo, foi um modelo murino de esporotricose subcutânea para analisar a extensão das lesões e a disseminação do patógeno. Os outros dois modelos, in vitro, foram utilizados para a análise da adesão das cepas em dois sistemas: matriz subendotelial nativa e, derme humana artificial. Para a realização destes experimentos, oito isolados foram selecionados: dois da espécie S. schenckii e seis da espécie S. brasiliensis. Os resultados mostraram que no modelo murino de esporotricose subcutânea, os isolados de S. brasiliensis mostraram-se mais virulentos do que os de S. schenckii. Em contrapartida, os isolados de S. schenckii apresentaram maior adesão à MEC e à derme humana artificial. Curiosamente, tanto os isolados de maior quanto os de menor virulência testados neste trabalho pertenciam à espécie S. brasiliensis. Devido à esta grande variabilidade encontrada nesta espécie, por exemplo, são necessários mais estudos para se poder correlacionar de forma segura o grau de virulência, a capacidade adesiva e a espécie patogênica do complexo Sporothrix.
Databáze: OpenAIRE