Effect of auristatin PHE on microtubule integrity and nuclear localization in Cryptococcus neoformans.
Effect of auristatin PHE on microtubule integrity and nuclear localization in Cryptococcus neoformans.
复制标题
auristatin PHE 对新生隐球菌微管完整性和核定位的影响。
DOI：
10.1128/aac.46.12.3802-3808.2002
复制
发表时间：
2002
影响因子：
4.9
通讯作者：
Pettit,RobinK
中科院分区：
文献类型：
--
作者：
Woyke,Tanja;Roberson,RobertW;Pettit,GeorgeR;Winkelmann,Günther;Pettit,RobinK
在新型隐球菌中研究了杀菌肽 auristatin PHE 的作用机制。由于 auristatin PHE 会导致 C 中的萌芽停滞。对新型隐球菌（T. Woyke、G. R. Pettit、G. Winkelmann 和 R. K. Pettit，Antimicrob. Agents Chemother.45：3580-3584，2001）、auristatin PHE 处理的细胞中的微管完整性和核定位进行了检查。与优化的 C 相结合的迭代反卷积。新型隐球菌微管免疫标记程序使得经 auristatin PHE 处理的 C 中微管细胞骨架的详细可视化成为可能。新型隐球菌。 auristatin PHE 对 C 的影响。将新型隐球菌微管组织与微管蛋白结合剂诺考达唑的微管组织进行比较。两种药物首先以时间和浓度依赖性方式完全破坏细胞质，然后破坏纺锤体微管。 auristatin PHE 的亚 MIC 在 4.5 小时内导致微管完全破坏，而需要 1.5 倍的诺考达唑 MIC 才能达到相同的效果。对于这两种药物，微管的破坏伴随着核迁移以及核和细胞分裂的阻断，导致细胞停滞在单核、大芽阶段。诺考达唑和线性肽奥瑞他汀 PHE 在结构和活性谱上显着不同，但在细胞水平上，它们具有相似的作用。
The mechanism of action of the fungicidal peptide auristatin PHE was investigated inCryptococcus neoformans. Since auristatin PHE causes budding arrest inC. neoformans(T. Woyke, G. R. Pettit, G. Winkelmann, and R. K. Pettit, Antimicrob. Agents Chemother.45:3580-3584, 2001), microtubule integrity and nuclear localization in auristatin PHE-treated cells were examined. Iterative deconvolution in conjunction with an optimizedC. neoformansmicrotubule immunolabeling procedure enabled detailed visualization of the microtubule cytoskeleton in auristatin PHE-treatedC. neoformans. The effect of auristatin PHE onC. neoformansmicrotubule organization was compared with that of the tubulin-binding agent nocodazole. Both drugs produced complete disruption first of cytoplasmic and then of spindle microtubules in a time- and concentration-dependent manner. Sub-MICs of auristatin PHE caused complete microtubule disruption within 4.5 h, while 1.5 times the nocodazole MIC was required for the same effect. For both drugs, disruption of microtubules was accompanied by blockage of nuclear migration and of nuclear and cellular division, resulting in cells arrested in a uninucleate, large-budded stage. Nocodazole and the linear peptide auristatin PHE are remarkably different in structure and spectrum of activity, yet on the cellular level, they have similar effects.