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 PMID:29740413  

Comparative Genomics Reveals the Regulatory Complexity of Bifidobacterial Arabinose and Arabino-Oligosaccharide Utilization.

Aleksandr A Arzamasov | Douwe van Sinderen | Dmitry A Rodionov
Frontiers in microbiology | 2018

Members of the genus Bifidobacterium are common inhabitants of the human gastrointestinal tract. Previously it was shown that arabino-oligosaccharides (AOS) might act as prebiotics and stimulate the bifidobacterial growth in the gut. However, despite the rapid accumulation of genomic data, the precise mechanisms by which these sugars are utilized and associated transcription control still remain unclear. In the current study, we used a comparative genomic approach to reconstruct arabinose and AOS utilization pathways in over 40 bacterial species belonging to the Bifidobacteriaceae family. The results indicate that the gene repertoire involved in the catabolism of these sugars is highly diverse, and even phylogenetically close species may differ in their utilization capabilities. Using bioinformatics analysis we identified potential DNA-binding motifs and reconstructed putative regulons for the arabinose and AOS utilization genes in the Bifidobacteriaceae genomes. Six LacI-family transcriptional factors (named AbfR, AauR, AauU1, AauU2, BauR1 and BauR2) and a TetR-family regulator (XsaR) presumably act as local repressors for AOS utilization genes encoding various α- or β-L-arabinofuranosidases and predicted AOS transporters. The ROK-family regulator AraU and the LacI-family regulator AraQ control adjacent operons encoding putative arabinose transporters and catabolic enzymes, respectively. However, the AraQ regulator is universally present in all Bifidobacterium species including those lacking the arabinose catabolic genes araBDA, suggesting its control of other genes. Comparative genomic analyses of prospective AraQ-binding sites allowed the reconstruction of AraQ regulons and a proposed binary repression/activation mechanism. The conserved core of reconstructed AraQ regulons in bifidobacteria includes araBDA, as well as genes from the central glycolytic and fermentation pathways (pyk, eno, gap, tkt, tal, galM, ldh). The current study expands the range of genes involved in bifidobacterial arabinose/AOS utilization and demonstrates considerable variations in associated metabolic pathways and regulons. Detailed comparative and phylogenetic analyses allowed us to hypothesize how the identified reconstructed regulons evolved in bifidobacteria. Our findings may help to improve carbohydrate catabolic phenotype prediction and metabolic modeling, while it may also facilitate rational development of novel prebiotics.

Pubmed ID: 29740413

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This is a list of tools and resources that we have found mentioned in this publication.


GenBank (tool)

RRID:SCR_002760

NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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SEED (tool)

RRID:SCR_002129

The SEED is a framework to support comparative analysis and annotation of genomes. The cooperative effort focuses on the development of the comparative genomics environment and, more importantly, on the development of curated genomic data. Curation of genomic data (annotation) is done via the curation of subsystems by an expert annotator across many genomes, not on a gene by gene basis. From the curated subsystems we extract a set of freely available protein families (FIGfams). These FIGfams form the core component of our RAST automated annotation technology. Answering numerous requests for automatic Seed-Quality annotations for more or less complete bacterial and archaeal genomes, we have established the free RAST-Server (RAST=Rapid Annotation using Subsytems Technology). Using similar technology, we make the Metagenomics-RAST-Server freely available. We also provide a SEED-Viewer that allows read-only access to the latest curated data sets. We currently have 58 Archaea, 902 Bacteria, 562 Eukaryota, 1254 Plasmids and 1713 Viruses in our database. All tools and datasets that make up the SEED are in the public domain and can be downloaded at ftp://ftp.theseed.org

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RegPrecise (tool)

RRID:SCR_002149

Collection of manually curated inferences of regulons in prokaryotic genomes. Database for capturing, visualization and analysis of transcription factor regulons that were reconstructed by comparative genomic approach in wide variety of prokaryotic genomes.

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UniProt (tool)

RRID:SCR_002380

Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.

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WEBLOGO (tool)

RRID:SCR_010236

Web application to generate sequence logos, graphical representations of patterns within multiple sequence alignment. Designed to make generation of sequence logos easy. Sequence logo generator.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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SeaView (tool)

RRID:SCR_015059

Graphical user interface for multiple sequence alignment and molecular phylogeny. SeaView also generates phylogenetic trees.

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SignalP (tool)

RRID:SCR_015644

Web application for prediction of the presence and location of signal peptide cleavage sites in amino acid sequences from different organisms. The method incorporates a prediction of cleavage sites and a signal peptide/non-signal peptide prediction based on a combination of several artificial neural networks.

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