GntR family of regulators in Mycobacterium smegmatis: a sequence and structure based characterization

Vindal, Vaibhav; Suma, Katta; Ranjan, Akash

doi:10.1186/1471-2164-8-289

Cited by 42 publications

(38 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GntR family members had an annotated GntR-type DNA-binding domain (IPR000524). Diverse regulators from the GntR family were divided into three subfamilies according to the previously described classification (17).…”

Section: Methodsmentioning

confidence: 99%

Transcription Factor Family-Based Reconstruction of Singleton Regulons and Study of the Crp/Fnr, ArsR, and GntR Families in Desulfovibrionales Genomes

et al. 2013

View full text Add to dashboard Cite

c Accurate detection of transcriptional regulatory elements is essential for high-quality genome annotation, metabolic reconstruction, and modeling of regulatory networks. We developed a computational approach for reconstruction of regulons operated by transcription factors (TFs) from large protein families and applied this novel approach to three TF families in 10 Desulfovibrionales genomes. Phylogenetic analyses of 125 regulators from the ArsR, Crp/Fnr, and GntR families revealed that 65% of these regulators (termed reference TFs) are well conserved in Desulfovibrionales, while the remaining 35% of regulators (termed singleton TFs) are species specific and show a mosaic distribution. For regulon reconstruction in the group of singleton TFs, the standard orthology-based approach was inefficient, and thus, we developed a novel approach based on the simultaneous study of all homologous TFs from the same family in a group of genomes. As a result, we identified binding for 21 singleton TFs and for all reference TFs in all three analyzed families. Within each TF family we observed structural similarities between DNA-binding motifs of different reference and singleton TFs. The collection of reconstructed regulons is available at the RegPrecise database (http://regprecise.lbl.gov/RegPrecise/Desulfovibrionales.jsp).

show abstract

Section: Methodsmentioning

confidence: 99%

Transcription Factor Family-Based Reconstruction of Singleton Regulons and Study of the Crp/Fnr, ArsR, and GntR Families in Desulfovibrionales Genomes

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Previous in silico sequence analysis of RoxY indicated that it belongs to the FadR subfamily of GntR regulators (39). GntR family regulators are often autoregulatory and found adjacent to genes that they control (15).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium smegmatis RoxY Is a Repressor ofoxySand Contributes to Resistance to Oxidative Stress and Bactericidal Ubiquitin-Derived Peptides

et al. 2011

View full text Add to dashboard Cite

The mycobactericidal properties of macrophages include the generation of reactive oxygen intermediates and the delivery of bacteria to a hydrolytic lysosome enriched in bactericidal ubiquitin-derived peptides (Ubpeptides). To better understand the interactions of ubiquitin-derived peptides with mycobacteria and identify putative mycobacterial intrinsic resistance mechanisms, we screened for transposon mutants with increased susceptibility to the bactericidal Ub-peptide Ub2. We isolated 27 Mycobacterium smegmatis mutants that were hypersusceptible to Ub2. Two mutants were isolated that possessed mutations in the msmeg_0166 gene, which encodes a transcriptional regulator. The msmeg_0166 mutants were also hypersusceptible to other host antimicrobial peptides and oxidative stress. In characterizing msmeg_0166, we found that it encodes a repressor of oxyS, and therefore we have renamed the gene roxY. We demonstrate that RoxY and OxyS contribute to M. smegmatis resistance to oxidative stress. An ahpD transposon mutant was also isolated in our screen for Ub-peptide hypersusceptibility. Overexpression of oxyS in M. smegmatis reduced transcription of the ahpCD genes, which encode a peroxide detoxification system. Our data indicate that RoxY, OxyS, and AhpD play a role in the mycobacterial oxidative stress response and are important for resistance to host antimicrobial peptides.Despite the availability of antibiotics to combat tuberculosis, it is one of the leading causes of death due to infectious disease. The World Health Organization estimates that Mycobacterium tuberculosis infects one-third of the world's population, and 8 million new cases of tuberculosis are reported annually (http://www.who.int/mediacentre/factsheets/fs104/en/). M. tuberculosis infections persist for decades despite the host immune response that exposes the bacterium to a number of stressful environments during the course of infection. The nature of these host defenses and the repertoire of M. tuberculosis resistance mechanisms are still being elucidated. The ability of M. tuberculosis to survive within the host macrophage is key to its pathogenesis. While the pathogen is well-equipped to establish a niche in resting macrophages, activation of the host macrophage shifts the balance toward mycobacterial clearance (26,38). The mycobactericidal activity of activated macrophages includes both oxidative and nonoxidative mechanisms. Studies with mice indicate that reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) function in control of tuberculosis infection: M. tuberculosis infection of NADPH phagosome oxidase (NOX2)-deficient mice indicates a role for ROI in the lung, and Nos2 Ϫ/Ϫ mice are quickly killed upon infection with M. tuberculosis (1,5,17). Enhanced fusion of the bacterium-containing vacuole with the macrophage lysosome also contributes to the mycobactericidal activity of activated macrophages. The induction of autophagy in Mycobacterium bovis BCG-and M. tuberculosis-infected macrophages by serum starvation, rapamy...

show abstract

“…Upstream region of mce2R possess novel conserved operator site Many FadR-like transcriptional regulators are reported to recognize DNA palindromes showing nucleotide preferences exhibited by members of FadR subfamily [9]. We analyzed DNA sequences for these preferences, in addition to conservation among the orthologous upstream region.…”

Section: Rv0586-orthologs Show a Similar Dna Binding Domainmentioning

confidence: 99%

“…Out of five FadRlike transcriptional regulators from M. tuberculosis, the regulators Rv0165c and Rv0586 are associated with mce1 and mce2 operon, respectively [7,8]. Typically, members of this subfamily of transcriptional regulators are known to be auto-regulatory [9]. Hence in addition to regulating expression of a number of genes and operons these regulators also regulate their own expression.…”

Section: Introductionmentioning

confidence: 99%

“…Based on known operator sites, members of this family of regulators were suggested to exhibit nucleotide preferences in their operator sites recognition. This study envisaged the nucleotide preferences in the upstream sequence of the putative mce2R gene along with the sequence conservation among the mycobacterial species [9,15]. Further, using recombinant Rv0586 protein, predicted DNA motifs were experimentally investigated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of operator sites within the upstream region of the putative mce2R gene from mycobacteria

2008

Self Cite

View full text Add to dashboard Cite

Mycobacterium tuberculosis harbors four mce operons. Among them, mce2 operon is preceded by a FadR-like regulator mce2R (Rv0586). Here, we report the operator sites of the mce2R and its orthologs in other sequenced mycobacteria and non-mycobacterial species Nocardia farciana. All the identified DNA motifs illustrate the FadR subfamily specific nucleotide preference. Moreover, these motifs from the upstream region share sequence conservation, which is in agreement with the similarity of their DNA binding domain. Using electrophoretic mobility shift assay, we demonstrate that the predicted DNA motifs specifically interact with the recombinant Mce2R-Rv0586. Our present study has implications in the understanding of cis-regulatory elements and the auto-regulatory nature of the FadR subfamily of regulators.

show abstract

GntR family of regulators in Mycobacterium smegmatis: a sequence and structure based characterization

Cited by 42 publications

References 38 publications

Transcription Factor Family-Based Reconstruction of Singleton Regulons and Study of the Crp/Fnr, ArsR, and GntR Families in Desulfovibrionales Genomes

Transcription Factor Family-Based Reconstruction of Singleton Regulons and Study of the Crp/Fnr, ArsR, and GntR Families in Desulfovibrionales Genomes

Mycobacterium smegmatis RoxY Is a Repressor ofoxySand Contributes to Resistance to Oxidative Stress and Bactericidal Ubiquitin-Derived Peptides

Identification of operator sites within the upstream region of the putative mce2R gene from mycobacteria

Contact Info

Product

Resources

About