Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients.
Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients.
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DOI：
10.1186/1471-2164-12-526
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发表时间：
2011-10-27
期刊：
影响因子：
4.4
通讯作者：
Kronstad JW
中科院分区：
文献类型：
--
作者：
Hu G;Wang J;Choi J;Jung WH;Liu I;Litvintseva AP;Bicanic T;Aurora R;Mitchell TG;Perfect JR;Kronstad JW
病原真菌通过大规模的基因组变化来适应寄主环境，这是一个很难描述的现象。新生隐球菌是HIV/AIDS患者真菌性脑膜脑炎的主要病因，我们最近发现了这种真菌的临床菌株，它们是13号染色体的二体。在这里，我们检测了单体和二体菌株的基因组可塑性和表型，并在最初的一组菌株中比较了它们在隐球菌病小鼠模型中的毒力，黑色素的产生与13号染色体上的单体相关，二体变种在小鼠中黑化程度较低，毒力减弱。在培养或通过小鼠传代后，发现了随后的菌株，它们的黑色素形成发生了变化，其他染色体的拷贝数也发生了变化。在某些菌株中观察到黑色素与13号染色体二体的相关性，但不是所有菌株。对培养中的环境和临床分离株的调查显示，很少出现二体染色体。然而，对从艾滋病患者脑脊液中新鲜收集并进行最低限度培养的分离株的检查提供了感染多种菌株和拷贝数变异的证据。总体而言，这些结果表明，新生葡萄球菌的基因组表现出比之前所认识到的更大程度的可塑性。此外，一种基本毒力因子的表达和疾病的严重程度与基因组变异有关。从艾滋病患者分离株中染色体变异的出现，结合观察到的二体对毒力的影响，表明基因组可塑性可能具有临床意义。
The adaptation of pathogenic fungi to the host environment via large-scale genomic changes is a poorly characterized phenomenon. Cryptococcus neoformans is the leading cause of fungal meningoencephalitis in HIV/AIDS patients, and we recently discovered clinical strains of the fungus that are disomic for chromosome 13. Here, we examined the genome plasticity and phenotypes of monosomic and disomic strains, and compared their virulence in a mouse model of cryptococcosis In an initial set of strains, melanin production was correlated with monosomy at chromosome 13, and disomic variants were less melanized and attenuated for virulence in mice. After growth in culture or passage through mice, subsequent strains were identified that varied in melanin formation and exhibited copy number changes for other chromosomes. The correlation between melanin and disomy at chromosome 13 was observed for some but not all strains. A survey of environmental and clinical isolates maintained in culture revealed few occurrences of disomic chromosomes. However, an examination of isolates that were freshly collected from the cerebrospinal fluid of AIDS patients and minimally cultured provided evidence for infections with multiple strains and copy number variation. Overall, these results suggest that the genome of C. neoformans exhibits a greater degree of plasticity than previously appreciated. Furthermore, the expression of an essential virulence factor and the severity of disease are associated with genome variation. The occurrence of chromosomal variation in isolates from AIDS patients, combined with the observed influence of disomy on virulence, indicates that genome plasticity may have clinical relevance.
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影响因子：
9.4
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