Importance of a developmentally regulated pheromone receptor of Cryptococcus neoformans for virulence

Importance of a developmentally regulated pheromone receptor of Cryptococcus neoformans for virulence
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DOI:
10.1128/iai.71.9.4953-4960.2003
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发表时间:
2003-09-01
影响因子:
3.1
通讯作者:
Kwon-Chung, KJ
Kwon-Chung, KJ
中科院分区:
医学2区
文献类型:
--
作者:
Chang, YC;Miller, GF;Kwon-Chung, KJ

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新型隐球菌是隐球菌病的病原体。在这种真菌中存在两种交配类型,MATalpha和MATa。C. neoformans是MATa株特异性基因,编码推定的七跨膜结构域信息素受体。与其他已报道的真菌信息素受体不同,CPRa具有功能多样性。CPRa的缺失会显著影响交配效率,但不会消除交配。CPRa的表达是发育调节的,不受转录调节因子STE12a缺失的影响。通过将培养物从液体培养基转移到固体培养基,CPRa的表达显著增加。CPRa在毒力方面也起着重要作用。Deltacpra细胞在小鼠大脑中产生的胶囊比野生型细胞小,感染Deltacpra的小鼠比接受野生型菌株的小鼠存活时间长得多。我们的研究结果表明,MATa信息素受体的C neoformans不仅需要交配,但也很重要的生存和生长的真菌在宿主组织。
Cryptococcus neoformans is the etiologic agent of cryptococcosis. Two mating types exist in this fungus, MATalpha and MATa. The CPRa gene of C. neoformans is a MATa strain-specific gene and encodes a putative seven-transmembrane domain pheromone receptor. Unlike the other reported fungal pheromone receptors, CPRa shows functional diversity. Deletion of CPRa drastically affects mating efficiency but does not abolish mating. CPRa expression is developmentally regulated and is not affected by deletion of the transcriptional regulator STE12a. The expression of CPRa is markedly increased by shifting cultures from liquid to solid media. CPRa also plays a significant role in virulence. Deltacpra cells produce smaller capsules in the brains of mice than the wild-type cells, and the mice infected with Deltacpra survive significantly longer than those receiving the wild-type strain. Our results suggest that the MATa pheromone receptor of C neoformans is not only required for mating but also important for survival and growth of the fungus in host tissue.