Mendes-Giannini Maria José Soares, Andreotti Patrícia Ferrari, Vincenzi Luciana Raquel, da Silva Juliana Leal Monteiro, Lenzi Henrique Leonel, Benard Gil, Zancopé-Oliveira Roseli, de Matos Guedes Herbert Leonel, Soares Christiane Pienna
Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, UNESP, R. Expedicionários do Brasil, 1621, 14802-901 Araraquara São Paulo, Brazil.
Microbes Infect. 2006 May;8(6):1550-9. doi: 10.1016/j.micinf.2006.01.012. Epub 2006 Apr 7.
Adhesion to extracellular matrix (ECM) proteins plays a crucial role in invasive fungal diseases. ECM proteins bind to the surface of Paracoccidioides brasiliensis yeast cells in distinct qualitative patterns. Extracts from Pb18 strain, before (18a) and after animal inoculation (18b), exhibited differential adhesion to ECM components. Pb18b extract had a higher capacity for binding to ECM components than Pb18a. Laminin was the most adherent component for both samples, followed by type I collagen, fibronectin, and type IV collagen for Pb18b. A remarkable difference was seen in the interaction of the two extracts with fibronectin and their fragments. Pb18b extract interacted significantly with the 120-kDa fragment. Ligand affinity binding assays showed that type I collagen recognized two components (47 and 80kDa) and gp43 bound both fibronectin and laminin. The peptide 1 (NLGRDAKRHL) from gp43, with several positively charged amino acids, contributed most to the adhesion of P. brasiliensis to Vero cells. Synthetic peptides derived from peptide YIGRS of laminin or from RGD of both laminin and fibronectin showed the greatest inhibition of adhesion of gp43 to Vero cells. In conclusion, this work provided new molecular details on the interaction between P. brasiliensis and ECM components.
与细胞外基质(ECM)蛋白的黏附在侵袭性真菌疾病中起着关键作用。ECM蛋白以不同的定性模式与巴西副球孢子菌酵母细胞表面结合。Pb18菌株在动物接种前(18a)和接种后(18b)的提取物对ECM成分表现出不同的黏附性。Pb18b提取物比Pb18a具有更高的与ECM成分结合的能力。层粘连蛋白是两个样品中最具黏附性的成分,其次对于Pb18b来说是I型胶原、纤连蛋白和IV型胶原。在两种提取物与纤连蛋白及其片段的相互作用中观察到显著差异。Pb18b提取物与120 kDa片段有显著相互作用。配体亲和结合试验表明,I型胶原识别两种成分(47 kDa和80 kDa),gp43与纤连蛋白和层粘连蛋白都结合。来自gp43的肽1(NLGRDAKRHL)含有几个带正电荷的氨基酸,对巴西副球孢子菌与Vero细胞的黏附贡献最大。源自层粘连蛋白的肽YIGRS或层粘连蛋白和纤连蛋白的RGD的合成肽对gp43与Vero细胞的黏附表现出最大的抑制作用。总之,这项工作提供了关于巴西副球孢子菌与ECM成分相互作用的新分子细节。