Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Characterization of the HNS Regulon Vibrio cholerae El Tor

ABSTRACT: The transcriptional factor ToxR initiates a virulence regulatory cascade required for V. cholerae to express critical host colonization factors and cause disease. Genome-wide expression studies suggest that ToxR regulates many genes important for V. cholerae pathogenesis, yet our knowledge of the direct regulon controlled by ToxR is limited to just four genes. Here, we determine ToxRâs genome-wide DNA-binding profile and show that ToxR is a global regulator of both progenitor genome-encoded genes and horizontally acquired islands encoding the majority of V. choleraeâs major virulence factors. Our results suggest that ToxR has gained regulatory control over important acquired elements that not only drive V. cholerae pathogenesis but that also define the major transitions of V. cholerae pandemic lineages. We demonstrate that ToxR shares nearly half its regulon with the histone-like nucleoid structuring protein H-NS, and antagonizes H-NS for control of critical colonization functions. This regulatory interaction is the major role of ToxR in V. cholerae colonization since deletion of H-NS abrogates the need of ToxR in V. cholerae host colonization. By comparing the genome-wide binding profiles of ToxR and other critical virulence regulators, we show that despite similar predicted DNA binding requirements, ToxR is unique in its global control of progenitor-encoded and acquired genes. Our results suggest that, like H-NS, factors in addition to linear DNA sequence drive selection of ToxR binding sites. We used ChIP-seq to identify HNS binding sites across the genome to determine the direct regulon of HNS

ORGANISM(S): Vibrio cholerae O1 str. C6706

SUBMITTER: Bryan Davies

PROVIDER: E-GEOD-72471 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Cholera is a diarrheal disease caused by Vibrio cholerae of serogroups O1 and O139 that affects impoverished populations worldwide. The histone-like nucleoid structuring protein (H-NS) is a global regulator of environmentally-regulated gene expression that plays a fundamental role in V. cholerae adaptation to disparate ecological niches. We used RNA-seq to characterize the hns transcriptome of El Tor biotype V. cholerae. H-NS affected the expression of 18% of all predicted genes in a growth phase-dependent manner. It silenced the transcription of genes encoding virulence regulators and cytotoxic factors such as the VieSAB regulatory system, the repeat in toxin (RTX) and hemolysin. H-NS was 10 times more effective in silencing the vieSAB promoter in El Tor compared to classical biotype V. cholerae. In the El Tor biotype hns mutant, VieSAB significantly enhanced the expression of cholera toxin genes. For the RTX and hemolysin, we found that overexpression of the transcription activator HlyU diminished H-NS occupancy at the hlyA promoter but not at the rtxCA and rtxBDE promoters. H-NS had a significant impact on the cell envelope and the mutant expressed elevated rpoE encoding the extracytoplamic sigma factor E (sE), though this effect was indirect. A remarkable feature of the hns transcriptome was the down-regulation of numerous methyl-accepting chemotaxis proteins in early stationary phase that translated into diminished chemotaxis toward the amino acids glycine and serine. Our study suggests that H-NS transcriptional silencing can contribute to multiple phenotypic differences observed between V. cholerae biotypes, mainly by differentially repressing the VieSAB sensory pathway. Transcriptome profiles of wild type and M-NM-^Thns mutant cells of the V. cholerae strain C7258 grown in LB medium were generated by Next Generation Sequencing using the Illumina HiSeq2000 platform. Samples from mid-exponential phase (OD600 0.5) and early stationary phase (OD600 2.0) were analyzed in duplicate

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Characterization of the HNS Regulon Vibrio cholerae El Tor

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