Clostridioides difficile SinR' regulates toxin, sporulation and motility through protein-protein interaction with SinR
Clostridioides difficile SinR' regulates toxin, sporulation and motility through protein-protein interaction with SinR
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DOI：
10.1016/j.anaerobe.2019.05.002
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发表时间：
2019-10-01
期刊：
影响因子：
2.3
通讯作者：
Govind, Revathi
中科院分区：
文献类型：
--
作者：
Ciftci, Yusuf;Girinathan, Brintha Parasumanna;Govind, Revathi
艰难梭菌是一种革兰氏阳性厌氧菌。已知C.艰难梭菌是抗生素相关性腹泻的主要原因之一。C.艰难梭菌是由细菌产生的高抗性孢子的结果。在枯草芽孢杆菌中，sin操纵子参与孢子形成抑制。两个蛋白质编码在这个操纵子，SinR和SinI，具有拮抗关系; SinR作为抑制剂孢子形成，而SinI抑制SinR的活性，从而使细菌孢子形成。在以前的研究中，我们研究了C。difficile，并将与该操纵子相关的两个基因命名为sinR和SinR '，类似于B中的sinR和sinI。subtilis，分别。我们已经表明，SinR和SinR'在发病途径中具有多效性作用，并且彼此拮抗地相互作用。不像B。subtilis SinI、SinR'在C.艰难梭菌携带两个结构域：HTH结构域和多聚化结构域（MD）。在这项研究中，我们首先进行了GST下拉实验，以确定与SinR相互作用的SinR'内的结构域。其次，这两个领域的影响，三个表型，孢子形成，运动，毒素生产进行了检查。本研究结果证实了SinR'的多聚化结构域（MD）负责SinR和SinR'之间的相互作用的预测。还发现SinR'主要通过多聚化结构域（MD）抑制SinR活性来调节孢子形成、毒素产生和运动性。(C)2019爱思唯尔有限公司版权所有。
Clostridioides difficile is a Gram-positive, anaerobic bacterium. It is known that C. difficile is one of the major causes of antibiotic associated diarrhea. The enhanced antibiotic resistance observed in C. difficile is the result of highly resistant spores produced by the bacterium. In Bacillus subtilis, the sin operon is involved in sporulation inhibition. Two proteins coded within this operon, SinR and SinI, have an antagonistic relationship; SinR acts as an inhibitor to sporulation whereas SinI represses the activity of SinR, thus allowing the bacterium to sporulate. In a previous study, we examined the sin locus in C. difficile and named the two genes associated with this operon sinR and SinR', analogous to sinR and sinI in B. subtilis, respectively. We have shown that SinR and SinR' have pleiotropic roles in pathogenesis pathways and interact antagonistically with each other. Unlike B. subtilis SinI, SinR' in C. difficile carries two domains: the HTH domain and the Multimerization Domain (MD). In this study, we first performed a GST Pull-down experiment to determine the domain within SinR' that interacts with SinR. Second, the effect of these two domains on three phenotypes; sporulation, motility, and toxin production was examined. The findings of this study confirmed the prediction that the Multimerization Domain (MD) of SinR' is responsible for the interaction between SinR and SinR'. It was also discovered that SinR' regulates sporulation, toxin production and motility primarily by inhibiting SinR activity through the Multimerization Domain (MD). (C) 2019 Elsevier Ltd. All rights reserved.