Steenbergen Judith N, Nosanchuk Joshua D, Malliaris Stephanie D, Casadevall Arturo
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,USA.
Infect Immun. 2003 Sep;71(9):4862-72. doi: 10.1128/IAI.71.9.4862-4872.2003.
Cryptococcus neoformans is an encapsulated, environmental fungus that can cause life-threatening meningitis. Pathogenicity of C. neoformans for macrophages and vertebrate hosts may be a mechanism selected in evolution for protection against environmental predators. In this study, we investigated whether Dictyostelium discoideum could serve as an alternate host for C. neoformans. D. discoideum has a defined genetic system which provides significant advantages for the study of fungus-amoeba interactions. Our results show that D. discoideum is susceptible to infection with C. neoformans and that the interactions are similar to those described previously for this fungus with macrophages and Acanthamoeba castellanii. Acapsular C. neoformans cells did not replicate when coincubated with D. discoideum. However, incubation of acapsular C. neoformans with D. discoideum mutants defective in myosin VII synthesis resulted in infection, validating the concept that avirulent organisms can be virulent in impaired hosts even at the unicellular level. Phagocytosis of C. neoformans by D. discoideum could be inhibited with capsule-specific antibodies and various sugars. Passage of an encapsulated C. neoformans strain through D. discoideum cultures increased virulence and was accompanied by larger capsules and faster time to melanization. These results add to the evidence implicating soil ameboid predators as important factors for the maintenance of C. neoformans virulence in the environment and suggest that D. discoideum promises to be an extremely useful system for studying the interaction of C. neoformans with phagocytic cells.
新型隐球菌是一种有荚膜的环境真菌，可引发危及生命的脑膜炎。新型隐球菌对巨噬细胞和脊椎动物宿主的致病性可能是在进化过程中选择的一种抵御环境捕食者的机制。在本研究中，我们调查了盘基网柄菌是否可作为新型隐球菌的替代宿主。盘基网柄菌有明确的遗传系统，这为研究真菌与变形虫的相互作用提供了显著优势。我们的结果表明，盘基网柄菌易受新型隐球菌感染，且这种相互作用与先前描述的该真菌与巨噬细胞及卡氏棘阿米巴的相互作用相似。无荚膜的新型隐球菌细胞与盘基网柄菌共孵育时不会增殖。然而，将无荚膜的新型隐球菌与肌球蛋白VII合成缺陷的盘基网柄菌突变体共孵育会导致感染，证实了无毒力的生物体即使在单细胞水平上在受损宿主中也可能具有毒力这一概念。盘基网柄菌对新型隐球菌的吞噬作用可被荚膜特异性抗体和各种糖类抑制。一株有荚膜的新型隐球菌菌株通过盘基网柄菌培养物传代后毒力增强，同时伴有更大的荚膜和更快的黑化时间。这些结果进一步证明土壤变形虫捕食者是新型隐球菌在环境中维持毒力的重要因素，并表明盘基网柄菌有望成为研究新型隐球菌与吞噬细胞相互作用的极为有用的系统。
