TARGETED GENE REPLACEMENT DEMONSTRATES THAT MYRISTOYL-COA/PROTEIN N-MYRISTOYLTRANSFERASE IS ESSENTIAL FOR VIABILITY OF CRYPTOCOCCUS-NEOFORMANS
TARGETED GENE REPLACEMENT DEMONSTRATES THAT MYRISTOYL-COA/PROTEIN N-MYRISTOYLTRANSFERASE IS ESSENTIAL FOR VIABILITY OF CRYPTOCOCCUS-NEOFORMANS
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DOI：
10.1073/pnas.91.25.12008
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发表时间：
1994-12-06
影响因子：
11.1
通讯作者：
GORDON, JI
中科院分区：
文献类型：
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作者：
LODGE, JK;JACKSONMACHELSKI, E;GORDON, JI
新型隐球菌（Cryptococcus neoformans）是引起免疫功能低下患者系统性真菌感染的主要原因。Myristoyl-CoA：protein N-myristoyltransferase（Nmt）催化肉豆蔻酸（C-14：0）从Myristoyl-CoA转移到新型隐球菌（Cryptococcus neoformans）营养生长过程中产生的一个细胞蛋白亚群的N-末端甘氨酸上。通过靶向基因置换治疗新生儿NMT。所得到的菌株是温度敏感的肉豆蔻酸营养缺陷型，当将它们置于缺乏肉豆蔻酸的培养基中时，它们在37 ℃下被杀死，并且在隐球菌脑膜炎的免疫抑制动物模型中，在初始感染的12天内从蛛网膜下腔完全消除。C、新生菌和人Nmt在它们的肽底物特异性方面表现出差异，这些差异可以用来开发一类新的杀真菌药物。
Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients, Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C-14:0) from myristoyl-CoA to the N-terminal glycine of a subset of cellular proteins produced during vegetative growth of C, neoformans, A Gly(487) --> Asp mutation was introduced into C. neoformans NMT by targeted gene replacement. The resulting strains are temperature-sensitive myristic acid auxotrophs, They are killed at 37 degrees C when placed in medium lacking myristate and, in an immunosuppressed animal model of cryptococcal meningitis, are completely eliminated from the subarachnoid space within 12 days of initial infection, C, neoformans and human Nmts exhibit differences in their peptide substrate specificities, These differences can be exploited to develop a new class of fungicidal drugs.