Mendes-Giannini M J, Taylor M L, Bouchara J B, Burger E, Calich V L, Escalante E D, Hanna S A, Lenzi H L, Machado M P, Miyaji M, Monteiro Da Silva J L, Mota E M, Restrepo A, Restrepo S, Tronchin G, Vincenzi L R, Xidieh C F, Zenteno E
Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP, Brazil.
Med Mycol. 2000;38 Suppl 1:113-23.
Most of our knowledge concerning the virulence determinants of pathogenic fungi comes from the infected host, mainly from animal models and more recently from in vitro studies with cell cultures. The fungi usually present intra- and/or extracellular host-parasite interfaces, with the parasitism phenomenon dependent on complementary surface molecules. Among living organisms, this has been characterized as a cohabitation event, where the fungus is able to recognize specific host tissues acting as an attractant, creating stable conditions for its survival. Several fungi pathogenic for humans and animals have evolved special strategies to deliver elements to their cellular targets that may be relevant to their pathogenicity. Most of these pathogens express surface factors that mediate binding to host cells either directly or indirectly, in the latter case binding to host adhesion components such as extracellular matrix (ECM) proteins, which act as 'interlinking' molecules. The entry of the pathogen into the host cell is initiated by fungal adherence to the cell surface, which generates an uptake signal that may induce its cytoplasmic internalization. Once this is accomplished, some fungi are able to alter the host cytoskeletal architecture, as manifested by a rearrangement of microtubule and microfilament proteins, and this can also induce epithelial host cells to become apoptotic. It is possible that fungal pathogens induce modulation of different host cell pathways in order to evade host defences and to foster their own proliferation. For a number of pathogens, the ability to bind ECM glycoproteins, the capability of internalization and the induction of apoptosis are considered important factors in virulence. Furthermore, specific recognition between fungal parasites and their host cell targets may be mediated by the interaction of carbohydrate-binding proteins, e.g., lectins on the surface of one type of cell, probably a parasite, that combine with complementary sugars on the surface of host-cell. These interactions supply precise models to study putative adhesins and receptor-containing molecules in the context of the fungus-host interface. The recognition of the host molecules by fungi such as Aspergillus fumigatus, Paracoccidioides brasiliensis and Histoplasma capsulatum, and their molecular mechanisms of adhesion and invasion, are reviewed in this paper.
我们关于致病真菌毒力决定因素的大部分知识来自受感染的宿主，主要来自动物模型，最近也来自细胞培养的体外研究。真菌通常呈现细胞内和/或细胞外的宿主 - 寄生虫界面，寄生现象依赖于互补的表面分子。在生物体中，这被描述为一种共生事件，其中真菌能够识别作为吸引物的特定宿主组织，为其生存创造稳定条件。几种对人类和动物致病的真菌已经进化出特殊策略，将可能与其致病性相关的成分传递到其细胞靶点。这些病原体中的大多数表达表面因子，这些表面因子直接或间接介导与宿主细胞的结合，在后一种情况下，与宿主粘附成分如细胞外基质（ECM）蛋白结合，这些蛋白充当“连接”分子。病原体进入宿主细胞是由真菌粘附到细胞表面引发的，这会产生一个摄取信号，可能诱导其细胞质内化。一旦完成这一步，一些真菌能够改变宿主细胞骨架结构，表现为微管和微丝蛋白的重新排列，这也可诱导上皮宿主细胞凋亡。真菌病原体可能诱导不同宿主细胞途径的调节，以逃避宿主防御并促进自身增殖。对于许多病原体来说，结合ECM糖蛋白的能力、内化能力和诱导凋亡被认为是毒力的重要因素。此外，真菌寄生虫与其宿主细胞靶点之间的特异性识别可能由碳水化合物结合蛋白的相互作用介导，例如一种细胞（可能是寄生虫）表面的凝集素与宿主细胞表面的互补糖结合。这些相互作用提供了精确的模型，用于在真菌 - 宿主界面的背景下研究假定的粘附素和含受体分子。本文综述了烟曲霉、巴西副球孢子菌和荚膜组织胞浆菌等真菌对宿主分子的识别及其粘附和侵袭的分子机制。
