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首页> 外文期刊>Infection and immunity >Identification of Novel Coxiella burnetii Icm/Dot Effectors and Genetic Analysis of Their Involvement in Modulating a Mitogen-Activated Protein Kinase Pathway
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Identification of Novel Coxiella burnetii Icm/Dot Effectors and Genetic Analysis of Their Involvement in Modulating a Mitogen-Activated Protein Kinase Pathway

机译：新型柯氏杆菌Icm /点效应子的鉴定及其参与调节丝裂原活化蛋白激酶途径的遗传分析

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Coxiella burnetii, the causative agent of Q fever, is a human intracellular pathogen that utilizes the Icm/Dot type IVB secretion system to translocate effector proteins into host cells. To identify novel C. burnetii effectors, we applied a machine-learning approach to predict C. burnetii effectors, and examination of 20 such proteins resulted in the identification of 13 novel effectors. To determine whether these effectors, as well as several previously identified effectors, modulate conserved eukaryotic pathways, they were expressed in Saccharomyces cerevisiae. The effects on yeast growth were examined under regular growth conditions and in the presence of caffeine, a known modulator of the yeast cell wall integrity (CWI) mitogen-activated protein (MAP) kinase pathway. In the presence of caffeine, expression of the effectors CBU0885 and CBU1676 caused an enhanced inhibition of yeast growth, and the growth inhibition of CBU0388 was suppressed. Furthermore, analysis of synthetic lethality effects and examination of the activity of the CWI MAP kinase transcription factor Rlm1 indicated that CBU0388 enhances the activation of this MAP kinase pathway in yeast, while CBU0885 and CBU1676 abolish this activation. Additionally, coexpression of CBU1676 and CBU0388 resulted in mutual suppression of their inhibition of yeast growth. These results strongly indicate that these three effectors modulate the CWI MAP kinase pathway in yeast. Moreover, both CBU1676 and CBU0885 were found to contain a conserved haloacid dehalogenase (HAD) domain, which was found to be required for their activity. Collectively, our results demonstrate that MAP kinase pathways are most likely targeted by C. burnetii Icm/Dot effectors.
机译：柯氏杆菌是Q热的病原体，是一种人类细胞内病原体，它利用Icm / Dot型IVB分泌系统将效应蛋白转运到宿主细胞中。为了鉴定新的伯氏梭菌效应子，我们应用了机器学习方法来预测伯氏梭菌效应子，并且对20种此类蛋白质的检查导致鉴定出13种新效应子。为了确定这些效应子以及几种先前鉴定的效应子是否能调节保守的真核途径，它们在酿酒酵母中表达。在常规生长条件下，在咖啡因的存在下，检查了对酵母生长的影响。咖啡因是酵母细胞壁完整性（CWI）丝裂原活化蛋白（MAP）激酶途径的已知调节剂。在咖啡因的存在下，效应子CBU0885和CBU1676的表达增强了对酵母生长的抑制，并且抑制了CBU0388的生长。此外，对合成致死作用的分析和对CWI MAP激酶转录因子Rlm1活性的检查表明，CBU0388增强了酵母中该MAP激酶途径的激活，而CBU0885和CBU1676取消了这种激活。另外，CBU1676和CBU0388的共表达导致相互抑制其对酵母生长的抑制。这些结果强烈表明这三个效应子调节酵母中的CWI MAP激酶途径。此外，发现CBU1676和CBU0885都含有一个保守的卤代酸脱卤酶（HAD）结构域，这被认为是其活性所必需的。总体而言，我们的结果表明MAP激酶途径最有可能被Burnetii Ccm / Dot效应子靶向。

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