Modulating Salmonella Typhimurium's Response to a Changing Environment through Bacterial Enhancer-Binding Proteins and the RpoN Regulon

Hartman, Christine E.; Samuels, David; Karls, Anna C.

doi:10.3389/fmolb.2016.00041

Cited by 17 publications

(9 citation statements)

References 75 publications

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“…Previous work with S. enterica serovar Typhimurium defined approximately 70 binding sites for RpoN. The binding sites were distributed around the chromosome, with more than half being within coding sequences [ 53, 54 ]. The Ori macrodomain has the most RpoN sites (17), while the other domains have approximately equal numbers: NSR (8), Right (10), Ter (11), Left (12) and NSL (12).…”

Section: Resultsmentioning

confidence: 99%

Broad-scale redistribution of mRNA abundance and transcriptional machinery in response to growth rate in Salmonella enterica serovar Typhimurium

Cameron

Dillon²,

Kröger

et al. 2017

Microbial Genomics

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We have investigated the connection between the four-dimensional architecture of the bacterial nucleoid and the organism's global gene expression programme. By localizing the transcription machinery and the transcriptional outputs across the genome of the model bacterium Salmonella enterica serovar Typhimurium at different stages of the growth cycle, a surprising disconnection between gene dosage and transcriptional output was revealed. During exponential growth, gene output occurred chiefly in the Ori (origin), Ter (terminus) and NSL (non-structured left) domains, whereas the Left macrodomain remained transcriptionally quiescent at all stages of growth. The apparently high transcriptional output in Ter was correlated with an enhanced stability of the RNA expressed there during exponential growth, suggesting that longer mRNA half-lives compensate for low gene dosage. During exponential growth, RNA polymerase (RNAP) was detected everywhere, whereas in stationary phase cells, RNAP was concentrated in the Ter macrodomain. The alternative sigma factors RpoE, RpoH and RpoN were not required to drive transcription in these growth conditions, consistent with their observed binding to regions away from RNAP and regions of active transcription. Specifically, these alternative sigma factors were found in the Ter macrodomain during exponential growth, whereas they were localized at the Ori macrodomain in stationary phase.

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Section: Resultsmentioning

confidence: 99%

Broad-scale redistribution of mRNA abundance and transcriptional machinery in response to growth rate in Salmonella enterica serovar Typhimurium

Cameron

Dillon²,

Kröger

et al. 2017

Microbial Genomics

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show abstract

“…This 'action at a distance' is mediated by integration host factor (IHF), which introduces a bend in the DNA, positioning bound FisR in close proximity to the promotor-bound RNA polymerase, with ATP hydrolysis stimulating open complex formation and transcription initiation (Hartman et al, 2016). The striking similarity to previous work (Luebke et al, 2014;Shimizu et al, 2017) is that FisR contains three conserved Cys residues (C53, C64 and C71) in the R domain and reduced FisR is activated by exposure to glutathione persulfide and inorganic polysulfide RSS (see Fig.…”

Section: Introductionmentioning

confidence: 99%

A new player in bacterial sulfide‐inducible transcriptional regulation

Giedroc

2017

Molecular Microbiology

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Summary Although hydrogen sulfide (H2S) is perhaps best known as a toxic gas, the electron-rich H2S functions as an energy source and electron donor for chemolithotrophic and photosynthetic bacteria, via sulfide oxidation, and is a universal substrate for cysteine biosynthesis. These distinct harmful and beneficial roles of H2S suggest the need to “sense” prevailing concentrations of sulfide and downstream reactive sulfur species (RSS) and regulate the expression of genes mediating sulfide homeostasis. The paper by Li et al. in this issue of Molecular Microbiology adds Cupriavidus FisR to an expanding repertoire of regulatory mechanisms that bacteria have evolved to sense cellular RSS and mitigate their deleterious effects.

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“…enhancer binding proteins (bEBPs), which activate the alternative transcription machinery directed by the alternative sigma factor 54 in response to diverse environmental stimuli (4,5). The ntr response allows cells to rapidly sense and adapt to nitrogen limitation; it does this by actively scavenging for alternative nitrogen sources through the transcriptional activation of genes encoding nitrogen source transporters, catabolic enzymes, and amino acid biosynthetic operons (1).…”

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confidence: 99%

Nitrogen Starvation Induces Persister Cell Formation in Escherichia coli

Brown

2019

J Bacteriol

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To cope with fluctuations in their environment, bacteria have evolved multiple adaptive stress responses. One such response is the nitrogen regulation stress response, which allows bacteria, such as Escherichia coli, to cope with and overcome conditions of nitrogen limitation. This response is directed by the two-component system NtrBC, where NtrC acts as the major transcriptional regulator to activate the expression of genes to mount the response. Recently, my colleagues and I showed that NtrC directly regulates the expression of the relA gene, the major (p)ppGpp synthetase in E. coli, coupling the nitrogen regulation stress and stringent responses. As elevated levels of (p)ppGpp have been implicated in the formation of persister cells, here, I investigated whether nitrogen starvation promotes their formation and whether the NtrC-RelA regulatory cascade plays a role. The results reveal that nitrogen-starved E. coli synthesizes (p)ppGpp and forms a higher percentage of persister cells than nonstarved cells and that both NtrC and RelA are important for these processes. This study provides novel insights into how the formation of persisters can be promoted in response to a nutritional stress. IMPORTANCE Bacteria often reside in environments where nutrient availability is scarce; therefore, they have evolved adaptive responses to rapidly cope with conditions of feast and famine. Understanding the mechanisms that underpin the regulation of how bacteria cope with this stress is a fundamentally important question in the wider context of understanding the biology of the bacterial cell and bacterial pathogenesis. Two major adaptive mechanisms to cope with starvation are the nitrogen regulation (ntr) stress and stringent responses. Here, I describe how these bacterial stress responses are coordinated under conditions of nitrogen starvation to promote the formation of antibiotic-tolerant persister cells by elevating levels of the secondary messenger (p)ppGpp.

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Modulating Salmonella Typhimurium's Response to a Changing Environment through Bacterial Enhancer-Binding Proteins and the RpoN Regulon

Cited by 17 publications

References 75 publications

Broad-scale redistribution of mRNA abundance and transcriptional machinery in response to growth rate in Salmonella enterica serovar Typhimurium

Broad-scale redistribution of mRNA abundance and transcriptional machinery in response to growth rate in Salmonella enterica serovar Typhimurium

A new player in bacterial sulfide‐inducible transcriptional regulation

Nitrogen Starvation Induces Persister Cell Formation in Escherichia coli

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