Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.
Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.
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DOI：
10.1371/journal.pone.0045083
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Perfect JR
中科院分区：
文献类型：
--
作者：
Tseng HK;Liu CP;Price MS;Jong AY;Chang JC;Toffaletti DL;Betancourt-Quiroz M;Frazzitta AE;Cho WL;Perfect JR
建立小鼠脑转移评估（MBTA），探讨隐球菌性脑膜脑炎的中枢神经系统发病机制。从109个预先选择的突变体中鉴定出两种隐球菌突变体，这些突变体都带有努尔塞乌霉素乙酰转移酶（NAT）抗性盒的特征标记。这两个突变体表现出异常的向中枢神经系统的转移。其中一种突变体在FNX1基因中含有零突变，而另一种突变体在RUB1基因中含有零突变，其向大脑的转运增加。池中的两个巨噬细胞粘附缺陷突变体12F1和3C9显示巨噬细胞吞噬减少，但在进入中枢神经系统时没有显示缺陷，这表明巨噬细胞内的转运（进入中枢神经系统的“特洛伊木马”模型）不是该MBTA中新生巨噬细胞迁移到中枢神经系统的主要机制。该研究设计为隐球菌如何通过血脑屏障（BBB）的遗传影响研究提供了一种新的策略，并且该实验中特异性分离突变体支持CNS进入的跨细胞机制。
A mouse brain transmigration assessment (MBTA) was created to investigate the central nervous system (CNS) pathogenesis of cryptococcal meningoencephalitis. Two cryptococcal mutants were identified from a pool of 109 pre-selected mutants that were signature-tagged with the nourseothricin acetyltransferase (NAT) resistance cassette. These two mutants displayed abnormal transmigration into the central nervous system. One mutant displaying decreased transmigration contains a null mutation in the putative FNX1 gene, whereas the other mutant possessing a null mutation in the putative RUB1 gene exhibited increased transmigration into the brain. Two macrophage adhesion-defective mutants in the pool, 12F1 and 3C9, showed reduced phagocytosis by macrophages, but displayed no defects in CNS entry suggesting that transit within macrophages (the “Trojan horse” model of CNS entry) is not the primary mechanism for C. neoformans migration into the CNS in this MBTA. This research design provides a new strategy for genetic impact studies on how Cryptococcus passes through the blood-brain barrier (BBB), and the specific isolated mutants in this assay support a transcellular mechanism of CNS entry.
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影响因子：
3.1
作者：
Lee, Anthony;Toffaletti, Dena L.;Perfect, John R.
通讯作者：
Perfect, John R.
影响因子：
64.5
作者：
Liu OW;Chun CD;Chow ED;Chen C;Madhani HD;Noble SM
通讯作者：
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影响因子：
3.1
作者：
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通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
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影响因子：
3.1
作者：
Cox, GM;Mukherjee, J;Perfect, JR
通讯作者：
Perfect, JR