Cryptococcus neoformans with a mutation in the tetratricopeptide repeat-containing gene, CCN1, causes subcutaneous lesions but fails to cause systemic infection
Cryptococcus neoformans with a mutation in the tetratricopeptide repeat-containing gene, CCN1, causes subcutaneous lesions but fails to cause systemic infection
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DOI：
10.1128/iai.71.4.1988-1994.2003
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发表时间：
2003-04-01
影响因子：
3.1
通讯作者：
Kwon-Chung, KJ
中科院分区：
文献类型：
--
作者：
Chung, S;Mondon, P;Kwon-Chung, KJ
我们研究了一种引起猫慢性鼻肉芽肿而无播散性疾病的新型隐球菌菌株。这种名为B-4551的菌株在高达35度的温度下生长，不会引起小鼠的全身感染。B-4551的许多细胞在猫鼻组织中形成短菌丝成分，在体外35℃条件下偶有形成。互补和序列分析显示，B-4551的温度敏感表型是由于隐球菌CCN1基因中赖氨酸残基的缺失所致。与野生型CCN1基因互补的B-4551在37℃下生长，并在小鼠中引起致命的全身感染。CCN1基因编码一种含有16个四三肽重复序列的蛋白质。CCN1与酿酒酵母CLF1基因同源，前者是mrna前剪接、细胞周期进程和DNA复制所必需的基因，后者与黑腹果蝇crn基因同源，后者参与神经发生。CLF1补充了B-4551的Ts表型。然而，CCN1未能拯救酿酒葡萄球菌中的clf1突变体。这些结果表明，Ccn1p在酵母中可能不像Clf1p那样具有功能多样性。
We studied a Cryptococcus neoformans strain that caused feline chronic nasal granuloma without disseminated disease. This strain, B-4551, grows at temperatures up to 35 degreesC and fails to cause systemic infection in mice. Many cells of B-4551 formed short hyphal elements in feline nasal tissue and occasionally at 35 degreesC in vitro. A complementation and sequence analysis revealed that the temperature-sensitive (TS) phenotype of B-4551 was due to deletion of a lysine residue in the cryptococcal CCN1 gene. B-4551 complemented with the wild type CCN1 gene grew at 37 C and caused fatal systemic infection in mice. The CCN1 gene encodes a protein containing 16 copies of a tetra tricopeptide repeat. CCN1 is homologous to the Saccharomyces cerevisiae CLF1 gene, which is required for pre-mRNA splicing, cell cycle progression, and DNA replication, and to the Drosophila melanogaster crn gene, which is involved in neurogenesis. CLF1 complemented the Ts phenotype of B-4551. CCN1, however, failed to rescue the clf1 mutant in S. cerevisiae. These results indicate that the Ccn1p may not be as functionally diverse as Clf1p in yeast.