Phenotypic switching in the human pathogenic fungus Cryptococcus neoformans is associated with changes in virulence and pulmonary inflammatory response in rodents
Phenotypic switching in the human pathogenic fungus Cryptococcus neoformans is associated with changes in virulence and pulmonary inflammatory response in rodents
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DOI：
10.1073/pnas.95.25.14967
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发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Casadevall, A
中科院分区：
文献类型：
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作者：
Goldman, DL;Fries, BC;Casadevall, A
在三株新型隐球菌中观察到集落形态的高频可逆变化，对于一株菌株（SB4，血清型A），这一过程产生了三种集落类型：光滑(S)，皱纹(W)和锯齿(C)，集落类型之间切换的频率因个体集落转换而异，最高可达10（-3）。感染W型菌落的小鼠比感染其他菌落的小鼠死亡更快。感染S、W和C型菌落的大鼠对感染的炎症反应为C > S > W，从C型感染的强烈肉芽肿性炎症伴cas样坏死到W型感染的轻微炎症，不同菌落类型的感染与大鼠对隐球菌蛋白的不同抗体反应相关。细胞特性分析揭示了三种菌落类型之间的差异。在另外两个菌株中也观察到菌落形态的高频变化。其中一株（24067A，血清型D）在光滑菌落和皱纹菌落之间发生切换。对于另一株（J32A，血清型A），在黏液和非黏液菌落之间发生切换。研究结果表明，新生隐杆线虫经历表型转换，这一过程可以影响毒力和宿主的炎症和免疫反应。表型转换可能在这种真菌逃避宿主防御和建立慢性感染的能力中发挥作用。
High-frequency reversible changes in colony morphology were observed in three strains of Cryptococcus neoformans, For one strain (SB4, serotype A), this process produced three colony types: smooth (S), wrinkled (W), and serrated (C), The frequency of switching between colony types varied for the individual colony transitions and was as high as 10(-3). Mice infected with colony type W died faster than those infected with other colony types, The rat inflammatory response to infection,vith colony types S, W, and C was C > S > W and ranged from intense granulomatous inflammation with caseous necrosis for infection with type C to minimal inflammation for infection with type W, Infection with the various colony types was associated with different antibody responses to cryptococcal proteins in rats. Analysis of cellular characteristics revealed differences between the three colony types. High-frequency changes in colony morphology were also observed in two additional strains of C. neoformans. For one strain (24067A, serotype D) the switching occurred between smooth and wrinkled colonies. For the other strain (J32A, serotype A), the switching occurred between mucoid and nonmucoid colonies. The findings indicate that C. neoformans undergoes phenotypic switching and that this process can affect virulence and host inflammatory and immune responses. Phenotypic switching may play a role in the ability of this fungus to escape host defenses and establish chronic infections.