Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto de Bioquímica Médica (IBqM), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Fungal Biol. 2017 Jun-Jul;121(6-7):602-614. doi: 10.1016/j.funbio.2017.04.002. Epub 2017 Apr 20.
Cryptococcus neoformans is an environmental fungus that can cause lethal meningoencephalitis in immunocompromised individuals. The mechanisms by which environmental microbes become pathogenic to mammals are still obscure, but different studies suggest that fungal virulence evolved from selection imposed by environmental predators. The soil-living Acanthamoeba castellanii is a well-known predator of C. neoformans. In this work, we evaluated the participation of C. neoformans virulence-associated structures in the interaction of fungal cells with A. castellanii. Fungal extracellular vesicles (EVs) and the polysaccharide glucuronoxylomannan (GXM) were internalized by A. castellanii with no impact on the viability of amoebal cells. EVs, but not free GXM, modulated antifungal properties of A. castellanii by inducing enhanced yeast survival. Phagocytosis of C. neoformans by amoebal cells and the pathogenic potential in a Galleria mellonella model were not affected by EVs, but previous interactions with A. castellanii rendered fungal cells more efficient in killing this invertebrate host. This observation was apparently associated with marked amoeba-induced changes in surface architecture and increased resistance to both oxygen- and nitrogen-derived molecular species. Our results indicate that multiple components with the potential to impact pathogenesis are involved in C. neoformans environmental interactions.
新生隐球菌是一种环境真菌，可在免疫功能低下的个体中引起致命性脑膜脑炎。环境微生物如何成为哺乳动物的病原体的机制尚不清楚，但不同的研究表明，真菌的毒力是由环境捕食者施加的选择进化而来的。土壤栖生的棘阿米巴原虫是新生隐球菌的一种著名捕食者。在这项工作中，我们评估了新生隐球菌与毒力相关的结构在真菌细胞与棘阿米巴原虫相互作用中的参与情况。真菌细胞外囊泡（EVs）和多糖葡聚糖（GXM）被棘阿米巴原虫内化，而不会影响阿米巴细胞的活力。EVs 但不是游离的 GXM 可通过诱导酵母存活增强来调节棘阿米巴原虫的抗真菌特性。噬菌作用和在大蜡螟模型中的致病性并没有被 EVs 影响，但与棘阿米巴原虫的先前相互作用使真菌细胞在杀死这种无脊椎动物宿主方面更有效率。这种观察结果显然与表面结构的明显的阿米巴诱导变化以及对氧和氮衍生的分子种类的抗性增加有关。我们的结果表明，与新生隐球菌的环境相互作用有关的多个具有潜在影响发病机制的成分参与其中。
