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首页> 外文期刊>Biochemistry >Sanguinarine Blocks Cytokinesis in Bacteria by Inhibiting FtsZ Assembly and Bundling
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Sanguinarine Blocks Cytokinesis in Bacteria by Inhibiting FtsZ Assembly and Bundling

机译：Sanguinarine通过抑制FTSZ组装和捆绑来阻断细菌中的细胞因子

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摘要

Bacterial diseases are among the leading causes of human death.The development of antibiotic resistance greatly contributes to the high mortality rate,and thus,the discovery of antibacterial drugs with novel mechanisms of action is needed.In this study,we found that sanguinarine,a benzophenanthridine alkaloid,strongly induced filamentation in both Gram-positive and Gram-negative bacteria and prevented bacterial cell division by inhibiting cytokinesis.Sanguinarine did not perturb the membrane structure in Escherichia coli.However,it perturbed the cytokinetic Z-ring formation in E.coli.In addition,sanguinarine strongly reduced the frequency of the occurrence of Z rings/micrometer of Bacillus subtilis length but did not alter the number of nucleoids/micrometer of cell length.The results suggested that sanguinarine inhibited cytokinesis in B.subtilis by inhibiting Z-ring formation without affecting nucleoid segregation.Sanguinarine inhibited the assembly of purified FtsZ and reduced the bundling of FtsZ protofilaments in vitro.Further,the interaction of sanguinarine to FtsZ was investigated using size-exclusion chromatography,an extrinsic fluorescent probe 1-anilinonaphthalene-8-sulfonic acid,and tryptophan fluorescence of mutated FtsZ (Y371W).Sanguinarine was found to bind to FtsZ with a dissociation constant of 18-30 mu M.The results together show that sanguinarine inhibits bacterial division by perturbing FtsZ assembly dynamics in the Z ring and provide evidence in support of the hypothesis that the assembly and bundling of FtsZ play a critical role in bacterial cytokinesis.The results suggest that sanguinarine may be used as a lead compound to develop FtsZ-targeted antibacterial agents.
机译：细菌疾病是人类死亡的主要原因。抗生素抗性的发展大大促进了高死亡率，因此，需要具有新的新作用机制的抗菌药物。在本研究中，我们发现anguinarine，a苯并苯蒽氨酸生物碱，强烈诱导革兰氏阳性和革兰氏阴性细菌的细菌和通过抑制细胞管内的细菌细胞分裂。血盲在大肠杆菌中没有扰乱膜结构。然而，它在大肠杆菌中扰乱了细胞内Z形环形成。在此外，血征强烈降低了苏黎霉长度的z环/千分尺的频率，但没有改变细胞长度的核心/微米的数量。结果表明，通过抑制Z-抑制血红素毒素抑制了B.subtinisis的细胞因子。无需影响核析偏析的环形形成。血征抑制了纯化的FTSZ组装并减少了BU使用尺寸排阻色谱法研究了FTSZ原型的FTSZ原丝的偏振，对血红素对FTSZ的相互作用，外部荧光探针1-苯胺萘-8-磺酸和突变FTSZ（Y371W）的色氨酸荧光。被发现结合FTSZ，分离常数为18-30μm。结果一起表明，Sanguinarine通过扰乱Z环中的FTSZ组装动力学来抑制细菌划分，并提供支持FTSZ的装配和捆绑起作用的假设的证据在细菌细胞因子中的作用。结果表明，Sanguinarine可以用作铅化合物以进行FtSZ靶向抗菌剂。

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  • 来源
    《Biochemistry》 |2005年第50期|共10页
  • 作者

    Tushar K.Beuria; Manas K.Santra; Dulal Panda;

  • 作者单位

    School of Biosciences and Bioengineering Indian Institute of Technology Bombay Mumbai 400076 India;

    School of Biosciences and Bioengineering Indian Institute of Technology Bombay Mumbai 400076 India;

    School of Biosciences and Bioengineering Indian Institute of Technology Bombay Mumbai 400076 India;

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  • 正文语种 eng
  • 中图分类 生物化学;
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