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首页> 外文期刊>Journal of bacteriology >Characterization of the Sporulation Initiation Pathway of Clostridium difficile and Its Role in Toxin Production
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Characterization of the Sporulation Initiation Pathway of Clostridium difficile and Its Role in Toxin Production

机译:艰难梭菌的孢子形成途径的表征及其在毒素产生中的作用

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Clostridium difficile is responsible for significant mortality and morbidity in the hospitalized elderly. C. difficile spores are infectious and are a major factor contributing to nosocomial transmission. The Spo0A response regulator is the master regulator for sporulation initiation and can influence many other cellular processes. Using the ClosTron gene knockout system, we inactivated genes encoding Spo0A and a putative sporulation-associated sensor histidine kinase in C. difficile. Inactivation of spo0A resulted in an asporogeneous phenotype, whereas inactivation of the kinase reduced C. difficle sporulation capacity by 3.5-fold, suggesting that this kinase also has a role in sporulation initiation. Furthermore, inactivation of either spo0A or the kinase resulted in a marked defect in C. difficile toxin production. Therefore, Spo0A and the signaling pathway that modulates its activity appear to be involved in regulation of toxin synthesis in C. difficile. In addition, Spo0A was directly phosphorylated by a putative sporulation-associated kinase, supporting the hypothesis that sporulation initiation in C. difficile is controlled by a two-component signal transduction system rather than a multicomponent phosphorelay. The implications of these findings for C. difficile sporulation, virulence, and transmission are discussed.
机译:艰难梭菌是造成住院老人的高死亡率和高发病率的原因。 C。难产孢子具有传染性,是导致医院内传播的主要因素。 Spo0A反应调节剂是启动孢子形成的主要调节剂,可影响许多其他细胞过程。使用ClosTron基因敲除系统,我们在 C中灭活了编码Spo0A和一个与孢子形成相关的传感器组氨酸激酶的基因。困难 spo0A 的失活导致了非孢子型的表型,而激酶的失活降低了 C的表现。顶芽的孢子形成能力增加了3.5倍,表明该激酶在孢子形成中也起作用。此外, spo0A 或激酶的失活导致 C的明显缺陷。难产毒素。因此,Spo0A及其调节其活性的信号传导途径似乎参与了 C毒素合成的调控。困难。此外,Spo0A被假定的孢子形成相关激酶直接磷酸化,支持了在 C中形成孢子的假设。难降解是由两组分信号转导系统而不是多组分磷光体控制的。这些发现对 C的意义。讨论了难产的孢子,毒力和传播。

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