Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
BMC Microbiol. 2011 Jun 20;11:141. doi: 10.1186/1471-2180-11-141.
Two ancestral nucleoid-associated proteins called Hha and YdgT contribute to the negative regulation of several virulence-associated genes in Salmonella enterica serovar Typhimurium. Our previous work showed that Hha and YdgT proteins are required for negative regulation of Salmonella Pathogenicity Island-2 and that hha ydgT double mutants are attenuated for murine infection. Interestingly, hha ydgT mutant bacteria exhibited a non-motile phenotype suggesting that Hha and YdgT have a role in flagellar regulation.
In this study we show that the non-motile phenotype of hha ydgT mutants is due to decreased levels of the master transcriptional regulator FlhD4C2 resulting in down-regulation of class II/III and class III flagellar promoters and lack of surface flagella on these cells. The horizontally acquired pefI-srgD region was found to be partially responsible for this phenotype since deletion of pefI-srgD in a hha ydgT deletion background resulted in transient restoration of class II/III and III transcription, expression of surface flagella, and motility in the quadruple mutant.
These data extend our current understanding of the mechanisms through which Hha and YdgT regulate flagellar biosynthesis and further describe how S. Typhimurium has integrated horizontal gene acquisitions into ancestral regulatory networks.
两种称为 Hha 和 YdgT 的祖先核相关蛋白有助于负调控沙门氏菌肠炎亚种 Typhimurium 中的几个毒力相关基因。我们之前的工作表明,Hha 和 YdgT 蛋白是负调控沙门氏菌致病岛 2 所必需的,并且 hha ydgT 双突变体在鼠感染中减弱。有趣的是,hha ydgT 突变体细菌表现出非运动表型,表明 Hha 和 YdgT 在鞭毛调节中具有作用。
在这项研究中,我们表明 hha ydgT 突变体的非运动表型是由于主转录调节因子 FlhD4C2 水平降低导致 II/III 类和 III 类鞭毛启动子下调以及这些细胞表面缺乏鞭毛。水平获得的 pefI-srgD 区部分负责这种表型,因为在 hha ydgT 缺失背景中缺失 pefI-srgD 导致四重突变体中 II/III 类和 III 类转录、表面鞭毛表达和运动的短暂恢复。
这些数据扩展了我们目前对 Hha 和 YdgT 调节鞭毛生物合成的机制的理解,并进一步描述了沙门氏菌如何将水平基因获取整合到祖先调控网络中。