ArticleProceedings of the National Academy of Sciences of the United States of America2008
A dual-signal regulatory circuit activates transcription of a set of divergent operons in Salmonella typhimurium.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 45 citations in OpenAlex.
- Molecular turn inEmerging microbes & infections · 2025Article
- Transcriptomic analysis using RNA sequencing and phenotypic analysis ofFrontiers in microbiology · 2024Article
- Nucleotides as Bacterial Second Messengers.Molecules (Basel, Switzerland) · 2023Review
- Two Additional Connections between the Transcriptional Programs Controlling Invasion and Intracellular Replication of Salmonella: HilD-SprB Positively RegulatesJournal of bacteriology · 2022Article
- Pathophysiology of enteropathogenicJournal of veterinary science · 2022Review
- Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp.Molecular microbiology · 2022Review
- How the PhoP/PhoQ System Controls Virulence and MgMicrobiology and molecular biology reviews : MMBR · 2021Review
- Emerging and divergent roles of pyrophosphorylated nucleotides in bacterial physiology and pathogenesis.PLoS pathogens · 2021Review
- The stringent response and physiological roles of (pp)pGpp in bacteria.Nature reviews. Microbiology · 2021Review
- MgrB Inactivation Confers Trimethoprim Resistance inFrontiers in microbiology · 2021Article
- Polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression in mycobacteria.Molecular microbiology · 2020Article
- Characterization of RelA in Acinetobacter baumannii.Journal of bacteriology · 2020Article
- An acid-tolerance response system protecting exponentially growing Escherichia coli.Nature communications · 2020Article
- SlyA Transcriptional Regulator Is Not Directly Affected by ppGpp Levels.Frontiers in microbiology · 2020Article
- Article
- Role of CsrA in stress responses and metabolism important for Salmonella virulence revealed by integrated transcriptomics.PloS one · 2019Article
- Threonine Phosphorylation Fine-Tunes the Regulatory Activity of Histone-Like Nucleoid Structuring Protein inFrontiers in microbiology · 2019Article
- HilD and PhoP independently regulate the expression of grhD1, a novel gene required for Salmonella Typhimurium invasion of host cells.Scientific reports · 2018Article
- Identification of new members of the Escherichia coli K-12 MG1655 SlyA regulon.Microbiology (Reading, England) · 2017Article
- Distinct innate responses are induced by attenuated Salmonella enterica serovar Typhimurium mutants.Cellular immunology · 2016Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
We present a molecular mechanism for signal transduction that activates transcription of the SlyA regulon in Salmonella typhimurium. We demonstrate that SlyA mediates transcriptional activation in response to guanosine tetraphosphate, ppGpp, according to the following observations: (i) in vivo transcription of SlyA-dependent genes is repressed when ppGpp is absent; this transcription can be restored by overproducing SlyA; (ii) in vivo dimerization and binding of SlyA to the target promoter are facilitated in the presence of ppGpp; and (iii) in vitro SlyA binding to the target promoter is enhanced when ppGpp is supplemented. Thus, ppGpp must be the cytoplasmic component that stimulates SlyA regulatory function by interacting directly with this regulator in Salmonella. This signaling domain, integrated by the PhoP/PhoQ 2-component system that activates slyA transcription by sensing Mg(2+), forms feedforward loops that regulate chromosomal loci identified through a motif search over the S. typhimurium genome. Many such loci are divergent operons, each formed by 2 neighboring genes in which transcription of these 2 loci proceeds in opposite directions. Both genes, however, are controlled by PhoP and SlyA through a single shared PhoP box and SlyA box present in their intergenic regions. A substitution in either box sequence causes a simultaneous cessation of transcription of a divergent operon, pagD-pagC, equivalent to the phenotype in a phoP or slyA mutant. We also identified several chromosomal loci that possess pagC-type genes without the cognate pagD-type genes. Therefore, our results provide a molecular basis for the understanding of SlyA-dependent phenotypes associated with Salmonella virulence.
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