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潜在致病性担子菌酵母的微管和肌动蛋白细胞骨架作为抗真菌药物的靶点

Microtubules and actin cytoskeleton of potentially pathogenic basidiomycetous yeast as targets for antifungals.

作者信息

Kopecká Marie, Gabriel Miroslav

机构信息

Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

出版信息

Chemotherapy. 2009;55(4):278-86. doi: 10.1159/000224655. Epub 2009 Jun 10.

DOI:10.1159/000224655
PMID:19521073
Abstract

BACKGROUND

The cytoskeleton was investigated as a potential target for the inhibition of cell division in Fellomyces fuzhouensis CBS 8243 related to Cryptococcus neoformans.

METHODS

Vincristine, vinblastine, paclitaxel, methyl benzimidazole-2-yl carbamate (BCM), thiabendazole, cytochalasins A, B and D and latrunculin A were added to yeast extract peptone dextrose medium containing cells, investigated by phase contrast and fluorescence microscopy, counted in a Burker chamber and absorbance was measured.

RESULTS

Vincristine, vinblastine, paclitaxel, cytochalasins A, B and D transiently blocked proliferation. BCM disrupted microtubules and inhibited mitosis, but F-actin patches and cables persisted and neck-less conidia appeared without stalks. Latrunculin disrupted F-actin, cells became spherical, and stalks and necks degenerated; microtubules persisted, but mitosis, cytokinesis and conidiogenesis were blocked. The combined application of latrunculin and BCM disrupted F-actin and microtubules, and inhibited cells became spherical and did not divide.

CONCLUSIONS

Microtubules and F-actin are effective targets for permanent inhibition of nuclear and cell division and conidiogenesis by BCM and latrunculin A.

摘要

背景

细胞骨架被作为与新型隐球菌相关的福州费洛蒙酵母CBS 8243中细胞分裂抑制的潜在靶点进行研究。

方法

将长春新碱、长春碱、紫杉醇、甲基苯并咪唑-2-基氨基甲酸酯(BCM)、噻苯达唑、细胞松弛素A、B和D以及拉春库林A添加到含有细胞的酵母提取物蛋白胨葡萄糖培养基中,通过相差显微镜和荧光显微镜进行观察,在血细胞计数板中计数并测量吸光度。

结果

长春新碱、长春碱、紫杉醇、细胞松弛素A、B和D可短暂阻断增殖。BCM破坏微管并抑制有丝分裂,但F-肌动蛋白斑块和束状结构持续存在,且出现无柄的无颈分生孢子。拉春库林破坏F-肌动蛋白,细胞变成球形,柄和颈部退化;微管持续存在,但有丝分裂、胞质分裂和分生孢子形成被阻断。拉春库林和BCM联合应用破坏F-肌动蛋白和微管,抑制细胞变成球形且不分裂。

结论

微管和F-肌动蛋白是BCM和拉春库林A永久抑制核分裂、细胞分裂和分生孢子形成的有效靶点。

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