Characterization of FarR as a highly specialized, growth phase-dependent transcriptional regulator in Neisseria meningitidis

Schielke, Stephanie; Spatz, Carolin; Schwarz, Roland F.; Joseph, Biju; Schoen, Christoph; Schulz, Sabine; Hubert, Kerstin; Frosch, Matthias; Schubert‐Unkmeir, Alexandra; Kurzai, Oliver

doi:10.1016/j.ijmm.2010.11.007

Cited by 8 publications

(11 citation statements)

References 58 publications

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“…Of the genes with an altered expression profile, NadR had the greatest effect on the nadA gene, which exhibited a Ͼ60-fold derepression in the NadR mutant. All other genes in the NadR regulon display much lower expression rate changes, in accordance with the previously described NadR targets (35).…”

Section: Discussionsupporting

confidence: 90%

“…It has been previously demonstrated that NadR binds to the nadA and farAB promoter regions (23,33), although no transcriptional regulation of farAB is thought to occur in meningococcus (33). Moreover, it has been recently reported that NadR-regulated genes were not directly bound by the protein (35), suggesting an indirect NadR regulation. To determine which of the NadR-repressed genes are under direct regulation of NadR, we amplified by PCR the upstream promoter regions of identified target genes and performed gel shift analysis with purified recombinant NadR.…”

Section: Resultsmentioning

confidence: 99%

“…This metabolite may act as a relevant niche signal to meningococci present in the oropharynx, which is bathed in saliva, for the induction of the NadA adhesin and other coregulated genes under NadR control. It has been in fact recently described that, even if being a highly specialized repressor of nadA, NadR can regulate, to a lesser extent, four other genes during exponential growth phase (35). In order to identify genes that may be coregulated with nadA by NadR and the 4HPA molecule, in this study we analyze the global gene expression profile of the wild-type and the NadR null mutant strains.…”

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confidence: 99%

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In the NadR Regulon, Adhesins and Diverse Meningococcal Functions Are Regulated in Response to Signals in Human Saliva

et al. 2012

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The Neisseria meningitidis regulator NadR was shown to repress expression of the NadA adhesin and play a major role in NadA phase-variable expression. In this study, we identified through microarray analysis over 30 genes coregulated with nadA in the NadR mutant and defined members of the NadR regulon through in vitro DNA-binding assays. Two distinct types of promoter architectures (I and II) were identified for NadR targets, differing in both the number and position of NadR-binding sites. All NadR-regulated genes investigated were found to respond to 4-hydroxyphenylacetic acid (4HPA), a small molecule secreted in human saliva, which was previously demonstrated to induce nadA expression by alleviating NadR-dependent repression. Interestingly, two types of NadR 4HPA responsive activities were found on different NadR targets corresponding to the two types of genes identified by different promoter architectures: while NadA and the majority of NadR targets (type I) are induced, only the MafA adhesins (type II) are corepressed in response to the same 4HPA signal. This alternate behavior of NadR was confirmed in a panel of strains in response to 4HPA and after incubation in saliva. The in vitro NadR binding activity at type I and type II promoter regions is differentially affected by 4HPA, suggesting that the nature of the NadR binding sites may define the regulation to which they will be subjected. We conclude that NadR coordinates a broad transcriptional response to signals present in human saliva, mimicked in vitro by 4HPA, enabling the meningococcus to adapt to the relevant host niche.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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In the NadR Regulon, Adhesins and Diverse Meningococcal Functions Are Regulated in Response to Signals in Human Saliva

et al. 2012

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“…Quantitative real-time PCR (qRT-PCR) analysis of the RNA samples described above was performed as described previously using the StepOnePlus system and the Power SYBR green Master Mix (53). nmb1567, encoding a putative membrane-associated peptidyl-prolyl isomerase, which was not differentially regulated in our microarray, was applied as endogenous control for data normalization.…”

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confidence: 99%

The Zinc-Responsive Regulon of Neisseria meningitidis Comprises 17 Genes under Control of a Zur Element

et al. 2012

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Zinc is a bivalent cation essential for bacterial growth and metabolism. The human pathogenNeisseria meningitidisexpresses a homologue of the Zinc uptake regulator Zur, which has been postulated to repress the putative zinc uptake protein ZnuD. In this study, we elucidated the transcriptome of meningococci in response to zinc by microarrays and quantitative real-time PCR (qRT-PCR). We identified 15 genes that were repressed and two genes that were activated upon zinc addition. All transcription units (genes and operons) harbored a putative Zur binding motif in their promoter regions. A meningococcal Zur binding consensus motif (Zur box) was deducedin silico, which harbors a conserved central palindrome consisting of hexameric inverted repeats separated by three nucleotides (TGTTATDNHATAACA).In vitrobinding of recombinant meningococcal Zur to this Zur box was shown for the first time using electrophoretic mobility shift assays. Zur binding to DNA depended specifically on the presence of zinc and was sensitive to mutations in the palindromic sequence. The Zur regulon among genes of unknown function comprised genes involved in zinc uptake, tRNA modification, and ribosomal assembly. In summary, this is the first study of the transcriptional response to zinc in meningococci.

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“…In N. gonorrhoeae, the regulon of OxyR, the transcriptional regulator controlling adaptation to oxidative stress, comprises only three genes, of which two are in an operon (28). In N. meningitidis, the regulon of FarA comprises only four genes, of which one, nadA, is strongly repressed (29-fold), while the other three genes are repressed at lower levels (Յ2-fold) (29).…”

Section: Discussionmentioning

confidence: 99%

Neisseria Prophage Repressor Implicated in Gonococcal Pathogenesis

Daou

McClure

et al. 2013

Infect Immun

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c Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, can infect and colonize multiple mucosal sites in both men and women. The ability to cope with different environmental conditions requires tight regulation of gene expression. In this study, we identified and characterized a gonococcal transcriptional regulatory protein (Neisseria phage repressor [Npr]) that was previously annotated as a putative gonococcal phage repressor protein. Npr was found to repress transcription of NGNG_00460 to NGNG_00463 (NGNG_00460-00463), an operon present within the phage locus Ngo⌽4. Npr binding sites within the NGNG_00460-00463 promoter region were found to overlap the ؊10 and ؊35 promoter motifs. A gonococcal npr mutant demonstrated increased adherence to and invasion of human endocervical epithelial cells compared to a wild-type gonococcal strain. Likewise, the gonococcal npr mutant exhibited enhanced colonization in a gonococcal mouse model of mucosal infection. Analysis of the gonococcal npr mutant using RNA sequence (RNA-seq) analysis demonstrated that the Npr regulon is limited to the operon present within the phage locus. Collectively, our studies have defined a new gonococcal phage repressor protein that controls the transcription of genes implicated in gonococcal pathogenesis.

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Characterization of FarR as a highly specialized, growth phase-dependent transcriptional regulator in Neisseria meningitidis

Cited by 8 publications

References 58 publications

In the NadR Regulon, Adhesins and Diverse Meningococcal Functions Are Regulated in Response to Signals in Human Saliva

In the NadR Regulon, Adhesins and Diverse Meningococcal Functions Are Regulated in Response to Signals in Human Saliva

The Zinc-Responsive Regulon of Neisseria meningitidis Comprises 17 Genes under Control of a Zur Element

Neisseria Prophage Repressor Implicated in Gonococcal Pathogenesis

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