NAEGLERIA-FOWLERI - CHARACTERIZATION OF A SECRETED HISTOLYTIC CYSTEINE PROTEASE
NAEGLERIA-FOWLERI - CHARACTERIZATION OF A SECRETED HISTOLYTIC CYSTEINE PROTEASE
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DOI：
10.1006/expr.1994.1023
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发表时间：
1994-03-01
影响因子：
2.1
通讯作者：
MCKERROW, J
中科院分区：
文献类型：
--
作者：
ALDAPE, K;HUIZINGA, H;MCKERROW, J
福氏耐格里菌是原发性阿米巴脑膜脑炎的病原体，这是一种罕见但迅速致命的人类疾病。它通过鼻粘膜和筛板侵入中枢神经系统。一旦进入脑组织，病菌会引起急性出血性坏死性脑膜脑炎。我们推测，寄生虫释放的蛋白酶有助于组织破坏和促进宿主入侵。N. Fowleri培养物揭示了一种主要的30-kDa蛋白酶，其具有与半胱氨酸蛋白酶一致的底物和抑制剂特异性。纯化酶的氨基端氨基酸序列分析表明，该酶是一种巯基蛋白酶，与组织蛋白酶L具有同源性。它在体外催化细胞外基质的降解，并对哺乳动物细胞有致细胞病变作用。Z-Phe-Ala-fluoromethyl ketone是一种不可逆的半胱氨酸蛋白酶抑制剂，可抑制阿米巴诱导的基质降解和细胞病变效应。结果表明，N. Fowleri分泌具有破坏宿主组织能力的半胱氨酸蛋白酶。非致病性物种Naegleria gruberi表达类似的蛋白酶，但与其致病性亲戚不同，其对30摄氏度以上的温度不耐热。(C)1994年出版社出版。
Naegleria fowleri is the etiologic agent of primary amebic meningoencephalitis, a rare but rapidly fatal disease of humans. It invades the central nervous system via nasal mucosa and cribriform plate. Once in brain tissue, the organism induces an acute hemorrhagic, necrotizing meningoencephalitis. We hypothesize that a protease released by the parasite contributes to tissue destruction and facilitates host invasion. Analysis of conditioned media of N. fowleri cultures revealed a major 30-kDa protease with substrate and inhibitor specificity consistent with cysteine proteases. Amino-terminal amino acid sequence of the purified enzyme showed it to be a thiol protease with homology to cathepsin L. It catalyzed the in vitro degradation of extracellular matrix and had a cytopathic effect on mammalian cells. Both ameba-induced matrix degradation and the cytopathic effect are inhibited by Z-Phe-Ala-fluoromethyl ketone, an irreversible cysteine protease inhibitor. Our results indicate that N. fowleri secretes a cysteine protease with the capacity to destroy host tissue. Naegleria gruberi, a nonpathogenic species, expresses a similar protease but, unlike its pathogenic relative, is not thermotolerant to temperatures above 30 degrees C. (C) 1994 Academic Press,Inc.