Abstract
BackgroundTwo 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.ResultsIn 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.ConclusionThese 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.
Highlights
Two ancestral nucleoid-associated proteins called Hha and YdgT contribute to the negative regulation of several virulence-associated genes in Salmonella enterica serovar Typhimurium
The increased pathogenic capacity conferred by such genes is dependent on their integration into ancestral regulatory networks of the cell, which can be accomplished by regulatory evolution following horizontal gene transfer [5]
Flagellar-based motility and surface flagellar expression is abolished in hha ydgT mutants During our characterization of Hha and YdgT-mediated repression of Salmonella Pathogenicity island 2 (SPI-2) genes, we noted that hha ydgT mutant bacteria settled to the bottom of standing culture tubes whereas wild type cultures remained turbid
Summary
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. The pathogenic nature of Salmonella enterica has been shaped by the horizontal acquisition of virulence determinants [1,2]. Typhimurium), many virulence genes are organized in mobile elements such as pathogenicity islands, prophages, and the Salmonella virulence plasmid [3,4]. The Hha/YmoA family of small nucleoid-associated proteins in Enterobacteriaceae [6] can participate in fine-tuning virulence gene expression in response to environmental cues [6,7].
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