Transcriptional regulation of NAD metabolism in bacteria: Genomic reconstruction of NiaR (YrxA) regulon

Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Nucleic Acids Research (Impact Factor: 9.11). 05/2008; 36(6):2032-46. DOI: 10.1093/nar/gkn046
Source: PubMed


A comparative genomic approach was used to reconstruct transcriptional regulation of NAD biosynthesis in bacteria containing orthologs of Bacillus subtilis gene yrxA, a previously identified niacin-responsive repressor of NAD de novo synthesis. Members of YrxA family (re-named here NiaR) are broadly conserved in the Bacillus/Clostridium group and in the deeply branching Fusobacteria and Thermotogales lineages. We analyzed upstream regions of genes associated with NAD biosynthesis to identify candidate NiaR-binding DNA motifs and assess the NiaR regulon content in these species. Representatives of the two distinct types of candidate NiaR-binding sites, characteristic of the Firmicutes and Thermotogales, were verified by an electrophoretic mobility shift assay. In addition to transcriptional control of the nadABC genes, the NiaR regulon in some species extends to niacin salvage (the pncAB genes) and includes uncharacterized membrane proteins possibly involved in niacin transport. The involvement in niacin uptake proposed for one of these proteins (re-named NiaP), encoded by the B. subtilis gene yceI, was experimentally verified. In addition to bacteria, members of the NiaP family are conserved in multicellular eukaryotes, including human, pointing to possible NaiP involvement in niacin utilization in these organisms. Overall, the analysis of the NiaR and NrtR regulons (described in the accompanying paper) revealed mechanisms of transcriptional regulation of NAD metabolism in nearly a hundred diverse bacteria.

Download full-text


Available from: Irina Rodionova,
  • Source
    • "The RegPrecise 3.0 contains 40 TF collections (an increase of 31 TFs since the previous database version) that include both widespread TFs such as NrdR, LexA and Zur present in more than 25 diverse taxonomic groups, and narrowly distributed TFs such as Irr in α-proteobacteria and PurR in γ-proteobacteria. Altogether, the orthologous TF collections include 443 regulogs that are valuable for comparative and evolutionary analysis of TF binding motifs and regulon contents, as illustrated by our previous publications on comparative genomics analyses of numerous TFs including HexR [11], Rex [14], NrdR [17], NrtR [30], NiaR [31], KdgR and ExuR [32], AraR and XylR [33], PsrA and LiuR [7], NsrR and NorR [16], Irr and IscR [18], BirA [34], and PaaR [35]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in prokaryotes is one of the critical tasks of modern genomics. Bacteria from different taxonomic groups, whose lifestyles and natural environments are substantially different, possess highly diverged transcriptional regulatory networks. The comparative genomics approaches are useful for in silico reconstruction of bacterial regulons and networks operated by both transcription factors (TFs) and RNA regulatory elements (riboswitches).DescriptionRegPrecise ( is a web resource for collection, visualization and analysis of transcriptional regulons reconstructed by comparative genomics. We significantly expanded a reference collection of manually curated regulons we introduced earlier. RegPrecise 3.0 provides access to inferred regulatory interactions organized by phylogenetic, structural and functional properties. Taxonomy-specific collections include 781 TF regulogs inferred in more than 160 genomes representing 14 taxonomic groups of Bacteria. TF-specific collections include regulogs for a selected subset of 40 TFs reconstructed across more than 30 taxonomic lineages. Novel collections of regulons operated by RNA regulatory elements (riboswitches) include near 400 regulogs inferred in 24 bacterial lineages. RegPrecise 3.0 provides four classifications of the reference regulons implemented as controlled vocabularies: 55 TF protein families; 43 RNA motif families; ~150 biological processes or metabolic pathways; and ~200 effectors or environmental signals. Genome-wide visualization of regulatory networks and metabolic pathways covered by the reference regulons are available for all studied genomes. A separate section of RegPrecise 3.0 contains draft regulatory networks in 640 genomes obtained by an conservative propagation of the reference regulons to closely related genomes. RegPrecise 3.0 gives access to the transcriptional regulons reconstructed in bacterial genomes. Analytical capabilities include exploration of: regulon content, structure and function; TF binding site motifs; conservation and variations in genome-wide regulatory networks across all taxonomic groups of Bacteria. RegPrecise 3.0 was selected as a core resource on transcriptional regulation of the Department of Energy Systems Biology Knowledgebase, an emerging software and data environment designed to enable researchers to collaboratively generate, test and share new hypotheses about gene and protein functions, perform large-scale analyses, and model interactions in microbes, plants, and their communities.
    BMC Genomics 11/2013; 14(1):745. DOI:10.1186/1471-2164-14-745 · 3.99 Impact Factor
  • Source
    • "However, in yeast, no specific NAm transporter has been identified as yet. Niacin transporters are known for bacteria; NiaP is involved in the uptake of both Na and NAm, and PnuC in that of NR (Rodionov et al., 2008a,b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: NAD+ plays multiple, essential roles in the cell. As a cofactor in many redox reactions it is key in the cellular energy metabolism and as a substrate it participates in many reactions leading to a variety of covalent modifications of enzymes with major roles in regulation of expression and metabolism. Cells may have the ability to produce this metabolite either via alternative de novo synthesis pathways and/or by different salvage pathways. In this issue of Molecular Microbiology, Gazanion et al. (2011) demonstrate that Leishmania species can only rely on the salvage of NAD+ building blocks. One of the enzymes involved, nicotinamidase, is absent from human cells. The enzyme is important for growth of Leishmania infantum and essential for establishing an infection. The crystal structure of the parasite protein has been solved and shows prospects for design of inhibitors to be used as leads for development of new drugs. Indeed, NAD+ metabolism is currently being considered as a promising drug target in various diseases and the vulnerability of Leishmania for interference of this metabolism has been proved in previous work by the same group, by showing that administration of NAD+ precursors has detrimental effect on the pathogenic, amastigote stage of this parasite.
    Molecular Microbiology 08/2011; 82(1):4-8. DOI:10.1111/j.1365-2958.2011.07810.x · 4.42 Impact Factor
  • Source
    • "L. solanacearum’ genome, we found only a few genes involved in vitamin uptake. There are no sequences matching complete transporters for riboflavin [27], [28], pyridoxal phosphate [29], niacin [30], cobalamin [29], [31], biotin [32], or folate [33], [34]. This is surprising for a few nutrients, as coding sequences associated with complete biosynthetic pathways for niacin, cobalamin, and pyridoxal phosphate are missing from the ZC-associated bacterium (Figure 4). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Zebra Chip (ZC) is an emerging plant disease that causes aboveground decline of potato shoots and generally results in unusable tubers. This disease has led to multi-million dollar losses for growers in the central and western United States over the past decade and impacts the livelihood of potato farmers in Mexico and New Zealand. ZC is associated with 'Candidatus Liberibacter solanacearum', a fastidious alpha-proteobacterium that is transmitted by a phloem-feeding psyllid vector, Bactericera cockerelli Sulc. Research on this disease has been hampered by a lack of robust culture methods and paucity of genome sequence information for 'Ca. L. solanacearum'. Here we present the sequence of the 1.26 Mbp metagenome of 'Ca. L. solanacearum', based on DNA isolated from potato psyllids. The coding inventory of the 'Ca. L. solanacearum' genome was analyzed and compared to related Rhizobiaceae to better understand 'Ca. L. solanacearum' physiology and identify potential targets to develop improved treatment strategies. This analysis revealed a number of unique transporters and pathways, all potentially contributing to ZC pathogenesis. Some of these factors may have been acquired through horizontal gene transfer. Taxonomically, 'Ca. L. solanacearum' is related to 'Ca. L. asiaticus', a suspected causative agent of citrus huanglongbing, yet many genome rearrangements and several gene gains/losses are evident when comparing these two Liberibacter. species. Relative to 'Ca. L. asiaticus', 'Ca. L. solanacearum' probably has reduced capacity for nucleic acid modification, increased amino acid and vitamin biosynthesis functionalities, and gained a high-affinity iron transport system characteristic of several pathogenic microbes.
    PLoS ONE 04/2011; 6(4):e19135. DOI:10.1371/journal.pone.0019135 · 3.23 Impact Factor
Show more