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Search Results: 1 - 10 of 53024 matches for " David Vallenet "
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Distinct co-evolution patterns of genes associated to DNA polymerase III DnaE and PolC
Stefan Engelen, David Vallenet, Claudine Médigue, Antoine Danchin
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-69
Abstract: Extending previous in silico heuristics for the analysis of gene co-evolution, we analyzed the function of genes clustering with dnaE and polC. Clusters were highly informative. DnaE co-evolves with the ribosome, the transcription machinery, the core of intermediary metabolism enzymes. It is also connected to the energy-saving enzyme necessary for RNA degradation, polynucleotide phosphorylase. Most of the proteins of this co-evolving set belong to the persistent set in bacterial proteomes, that is fairly ubiquitously distributed. In contrast, PolC co-evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade, suggesting at least two origins for the degradosome.DNA replication involves two machineries, DnaE and PolC. DnaE co-evolves with the core functions of bacterial life. In contrast PolC co-evolves with a set of RNA degradation enzymes that does not derive from the degradosome identified in gamma-Proteobacteria. This suggests that at least two independent RNA degradation pathways existed in the progenote community at the end of the RNA genome world.Future developments of Synthetic Biology require that patterns of gene organization in genomes are carefully taken into account [1]. Following the pioneering work of Sueoka [2], Lobry and co-workers identified a replication-linked bias in the nucleotide distribution in bacterial chromosomes. Subsequently, a bias in favor of genes transcribed in the same direction as that of the movement of the replication fork was observed in most bacterial genomes [3,4]. The bias was correlated with the presence in the genome of a single origin of replication. Taken together, these observations led to the construction of algorithms meant to identify in silico the origins of replication [5]. The cause of the bias has been a matter of speculation until it was observed that Firmicutes displayed the strongest bias [6,7] reaching 87% in organisms such as Thermoanaerobacter tengcongensis [8]. A first hypothe
The CanOE Strategy: Integrating Genomic and Metabolic Contexts across Multiple Prokaryote Genomes to Find Candidate Genes for Orphan Enzymes
Adam Alexander Thil Smith ,Eugeni Belda,Alain Viari,Claudine Medigue,David Vallenet
PLOS Computational Biology , 2012, DOI: 10.1371/journal.pcbi.1002540
Abstract: Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes), a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short). The first step locates “genomic metabolons”, i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12.
Comparative Genomics of Multidrug Resistance in Acinetobacter baumannii.
Fournier,Vallenet,Barbe,Audic
PLOS Genetics , 2006,
Abstract: Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria commonly found in water and soil. This organism was susceptible to most antibiotics in the 1970s. It has now become a major cause of hospital-acquired infections worldwide due to its remarkable propensity to rapidly acquire resistance determinants to a wide range of antibacterial agents. Here we use a comparative genomic approach to identify the complete repertoire of resistance genes exhibited by the multidrug-resistant A. baumannii strain AYE, which is epidemic in France, as well as to investigate the mechanisms of their acquisition by comparison with the fully susceptible A. baumannii strain SDF, which is associated with human body lice. The assembly of the whole shotgun genome sequences of the strains AYE and SDF gave an estimated size of 3.9 and 3.2 Mb, respectively. A. baumannii strain AYE exhibits an 86-kb genomic region termed a resistance island-the largest identified to date-in which 45 resistance genes are clustered. At the homologous location, the SDF strain exhibits a 20 kb-genomic island flanked by transposases but devoid of resistance markers. Such a switching genomic structure might be a hotspot that could explain the rapid acquisition of resistance markers under antimicrobial pressure. Sequence similarity and phylogenetic analyses confirm that most of the resistance genes found in the A. baumannii strain AYE have been recently acquired from bacteria of the genera Pseudomonas, Salmonella, or Escherichia. This study also resulted in the discovery of 19 new putative resistance genes. Whole-genome sequencing appears to be a fast and efficient approach to the exhaustive identification of resistance genes in epidemic infectious agents of clinical significance.
A Novel Acyl-CoA Beta-Transaminase Characterized from a Metagenome
Alain Perret, Christophe Lechaplais, Sabine Tricot, Nadia Perchat, Carine Vergne, Christine Pellé, Karine Bastard, Annett Kreimeyer, David Vallenet, Anne Zaparucha, Jean Weissenbach, Marcel Salanoubat
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022918
Abstract: Background Bacteria are key components in all ecosystems. However, our knowledge of bacterial metabolism is based solely on the study of cultivated organisms which represent just a tiny fraction of microbial diversity. To access new enzymatic reactions and new or alternative pathways, we investigated bacterial metabolism through analyses of uncultivated bacterial consortia. Methodology/Principal Findings We applied the gene context approach to assembled sequences of the metagenome of the anaerobic digester of a municipal wastewater treatment plant, and identified a new gene which may participate in an alternative pathway of lysine fermentation. Conclusions We characterized a novel, unique aminotransferase that acts exclusively on Coenzyme A (CoA) esters, and proposed a variant route for lysine fermentation. Results suggest that most of the lysine fermenting organisms use this new pathway in the digester. Its presence in organisms representative of two distinct bacterial divisions indicate that it may also be present in other organisms.
NeMeSys: a biological resource for narrowing the gap between sequence and function in the human pathogen Neisseria meningitidis
Christophe Rusniok, David Vallenet, Stéphanie Floquet, Helen Ewles, Coralie Mouzé-Soulama, Daniel Brown, Aurélie Lajus, Carmen Buchrieser, Claudine Médigue, Philippe Glaser, Vladimir Pelicic
Genome Biology , 2009, DOI: 10.1186/gb-2009-10-10-r110
Abstract: By determining and manually annotating the complete genome sequence of a serogroup C clinical isolate of N. meningitidis (strain 8013) and assembling a library of defined mutants in up to 60% of its non-essential genes, we have created NeMeSys, a biological resource for Neisseria meningitidis systematic functional analysis. To further enhance the versatility of this toolbox, we have manually (re)annotated eight publicly available Neisseria genome sequences and stored all these data in a publicly accessible online database. The potential of NeMeSys for narrowing the gap between sequence and function is illustrated in several ways, notably by performing a functional genomics analysis of the biogenesis of type IV pili, one of the most widespread virulence factors in bacteria, and by identifying through comparative genomics a complete biochemical pathway (for sulfur metabolism) that may potentially be important for nasopharyngeal colonization.By improving our capacity to understand gene function in an important human pathogen, NeMeSys is expected to contribute to the ongoing efforts aimed at understanding a prokaryotic cell comprehensively and eventually to the design of new therapies.By revealing complete repertoires of genes, genome sequences provide the key to a better and eventually global understanding of the biology of living organisms. It is widely accepted that this will have important consequences on human health and economics by leading to the rational design of novel therapies against pathogens infecting humans, livestock or crops [1]. For example, identifying genes essential for cell viability or pathogenesis would uncover targets for new antibiotics or drugs that selectively interfer with virulence mechanisms of pathogenic species, respectively. The major obstacle to this is the fact that hundreds of predicted coding sequences (CDSs) in every genome remain uncharacterized. Unraveling gene function on such a large scale requires suitable biological resources
Comparative Genomics of Aeschynomene Symbionts: Insights into the Ecological Lifestyle of Nod-Independent Photosynthetic Bradyrhizobia
Damien Mornico,Lucie Miché,Gilles Béna,Nico Nouwen,André Verméglio,David Vallenet,Alexander A.T. Smith,Eric Giraud,Claudine Médigue,Lionel Moulin
Genes , 2012, DOI: 10.3390/genes3010035
Abstract: Tropical aquatic species of the legume genus Aeschynomene are stem- and root-nodulated by bradyrhizobia strains that exhibit atypical features such as photosynthetic capacities or the use of a nod gene-dependent (ND) or a nod gene-independent (NI) pathway to enter into symbiosis with legumes. In this study we used a comparative genomics approach on nine Aeschynomene symbionts representative of their phylogenetic diversity. We produced draft genomes of bradyrhizobial strains representing different phenotypes: five NI photosynthetic strains (STM3809, ORS375, STM3847, STM4509 and STM4523) in addition to the previously sequenced ORS278 and BTAi1 genomes, one photosynthetic strain ORS285 hosting both ND and NI symbiotic systems, and one NI non-photosynthetic strain (STM3843). Comparative genomics allowed us to infer the core, pan and dispensable genomes of Aeschynomene bradyrhizobia, and to detect specific genes and their location in Genomic Islands (GI). Specific gene sets linked to photosynthetic and NI/ND abilities were identified, and are currently being studied in functional analyses.
Iterative reconstruction of a global metabolic model of Acinetobacter baylyi ADP1 using high-throughput growth phenotype and gene essentiality data
Maxime Durot, Fran?ois Le Fèvre, Véronique de Berardinis, Annett Kreimeyer, David Vallenet, Cyril Combe, Serge Smidtas, Marcel Salanoubat, Jean Weissenbach, Vincent Schachter
BMC Systems Biology , 2008, DOI: 10.1186/1752-0509-2-85
Abstract: We reconstructed a constraint-based metabolic model of Acinetobacter baylyi ADP1, a soil bacterium of interest for environmental and biotechnological applications with large-spectrum biodegradation capabilities. Following initial reconstruction from genome annotation and the literature, we iteratively refined the model by comparing its predictions with the results of large-scale experiments: (1) high-throughput growth phenotypes of the wild-type strain on 190 distinct environments, (2) genome-wide gene essentialities from a knockout mutant library, and (3) large-scale growth phenotypes of all mutant strains on 8 minimal media. Out of 1412 predictions, 1262 were initially consistent with our experimental observations. Inconsistencies were systematically examined, leading in 65 cases to model corrections. The predictions of the final version of the model, which included three rounds of refinements, are consistent with the experimental results for (1) 91% of the wild-type growth phenotypes, (2) 94% of the gene essentiality results, and (3) 94% of the mutant growth phenotypes. To facilitate the exploitation of the metabolic model, we provide a web interface allowing online predictions and visualization of results on metabolic maps.The iterative reconstruction procedure led to significant model improvements, showing that genome-wide mutant phenotypes on several media can significantly facilitate the transition from genome annotation to a high-quality model.The diversity of bacterial metabolism and the perspective of engineering applications has spurred a steep increase in both the number of sequencing projects and the volume of high throughput experiments on bacteria. The need to interpret and integrate these datasets at the systems level has triggered the development of model-based computational methods [1]. Among them, the constraint-based modeling approach (CBM) has proved to be particularly efficient at integrating large-scale omics datasets related to metabolism, su
Comparative Genomics of Multidrug Resistance in Acinetobacter baumannii
Pierre-Edouard Fournier ,David Vallenet,Valérie Barbe,Stéphane Audic,Hiroyuki Ogata,Laurent Poirel,Hervé Richet,Catherine Robert,Sophie Mangenot,Chantal Abergel,Patrice Nordmann,Jean Weissenbach,Didier Raoult,Jean-Michel Claverie
PLOS Genetics , 2006, DOI: 10.1371/journal.pgen.0020007
Abstract: Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria commonly found in water and soil. This organism was susceptible to most antibiotics in the 1970s. It has now become a major cause of hospital-acquired infections worldwide due to its remarkable propensity to rapidly acquire resistance determinants to a wide range of antibacterial agents. Here we use a comparative genomic approach to identify the complete repertoire of resistance genes exhibited by the multidrug-resistant A. baumannii strain AYE, which is epidemic in France, as well as to investigate the mechanisms of their acquisition by comparison with the fully susceptible A. baumannii strain SDF, which is associated with human body lice. The assembly of the whole shotgun genome sequences of the strains AYE and SDF gave an estimated size of 3.9 and 3.2 Mb, respectively. A. baumannii strain AYE exhibits an 86-kb genomic region termed a resistance island—the largest identified to date—in which 45 resistance genes are clustered. At the homologous location, the SDF strain exhibits a 20 kb-genomic island flanked by transposases but devoid of resistance markers. Such a switching genomic structure might be a hotspot that could explain the rapid acquisition of resistance markers under antimicrobial pressure. Sequence similarity and phylogenetic analyses confirm that most of the resistance genes found in the A. baumannii strain AYE have been recently acquired from bacteria of the genera Pseudomonas, Salmonella, or Escherichia. This study also resulted in the discovery of 19 new putative resistance genes. Whole-genome sequencing appears to be a fast and efficient approach to the exhaustive identification of resistance genes in epidemic infectious agents of clinical significance.
Ralstonia syzygii, the Blood Disease Bacterium and Some Asian R. solanacearum Strains Form a Single Genomic Species Despite Divergent Lifestyles
Beno?t Remenant, Jean-Charles de Cambiaire, Gilles Cellier, Jonathan M. Jacobs, Sophie Mangenot, Valérie Barbe, Aurélie Lajus, David Vallenet, Claudine Medigue, Mark Fegan, Caitilyn Allen, Philippe Prior
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024356
Abstract: The Ralstonia solanacearum species complex includes R. solanacearum, R. syzygii, and the Blood Disease Bacterium (BDB). All colonize plant xylem vessels and cause wilt diseases, but with significant biological differences. R. solanacearum is a soilborne bacterium that infects the roots of a broad range of plants. R. syzygii causes Sumatra disease of clove trees and is actively transmitted by cercopoid insects. BDB is also pathogenic to a single host, banana, and is transmitted by pollinating insects.?Sequencing and DNA-DNA hybridization studies indicated that despite their phenotypic differences, these three plant pathogens are actually very closely related, falling into the Phylotype IV subgroup of the R. solanacearum species complex. To better understand the relationships among these bacteria, we sequenced and annotated the genomes of R. syzygii strain R24 and BDB strain R229. These genomes were compared to strain PSI07, a closely related Phylotype IV tomato isolate of R. solanacearum, and to five additional R. solanacearum genomes. Whole-genome comparisons confirmed previous phylogenetic results: the three phylotype IV strains share more and larger syntenic regions with each other than with other R. solanacearum strains. Furthermore, the genetic distances between strains, assessed by an in-silico equivalent of DNA-DNA hybridization, unambiguously showed that phylotype IV strains of BDB, R. syzygii and R. solanacearum form one genomic species. Based on these comprehensive data we propose a revision of the taxonomy of the R. solanacearum species complex. The BDB and R. syzygii genomes encoded no obvious unique metabolic capacities and contained no evidence of horizontal gene transfer from bacteria occupying similar niches. Genes specific to R. syzygii and BDB were almost all of unknown function or extrachromosomal origin. Thus, the pathogenic life-styles of these organisms are more probably due to ecological adaptation and genomic convergence during vertical evolution than to the acquisition of DNA by horizontal transfer.
Comparative Analysis of Acinetobacters: Three Genomes for Three Lifestyles
David Vallenet, Patrice Nordmann, Valérie Barbe, Laurent Poirel, Sophie Mangenot, Elodie Bataille, Carole Dossat, Shahinaz Gas, Annett Kreimeyer, Patricia Lenoble, Sophie Oztas, Julie Poulain, Béatrice Segurens, Catherine Robert, Chantal Abergel, Jean-Michel Claverie, Didier Raoult, Claudine Médigue, Jean Weissenbach, Stéphane Cruveiller
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001805
Abstract: Acinetobacter baumannii is the source of numerous nosocomial infections in humans and therefore deserves close attention as multidrug or even pandrug resistant strains are increasingly being identified worldwide. Here we report the comparison of two newly sequenced genomes of A. baumannii. The human isolate A. baumannii AYE is multidrug resistant whereas strain SDF, which was isolated from body lice, is antibiotic susceptible. As reference for comparison in this analysis, the genome of the soil-living bacterium A. baylyi strain ADP1 was used. The most interesting dissimilarities we observed were that i) whereas strain AYE and A. baylyi genomes harbored very few Insertion Sequence elements which could promote expression of downstream genes, strain SDF sequence contains several hundred of them that have played a crucial role in its genome reduction (gene disruptions and simple DNA loss); ii) strain SDF has low catabolic capacities compared to strain AYE. Interestingly, the latter has even higher catabolic capacities than A. baylyi which has already been reported as a very nutritionally versatile organism. This metabolic performance could explain the persistence of A. baumannii nosocomial strains in environments where nutrients are scarce; iii) several processes known to play a key role during host infection (biofilm formation, iron uptake, quorum sensing, virulence factors) were either different or absent, the best example of which is iron uptake. Indeed, strain AYE and A. baylyi use siderophore-based systems to scavenge iron from the environment whereas strain SDF uses an alternate system similar to the Haem Acquisition System (HAS). Taken together, all these observations suggest that the genome contents of the 3 Acinetobacters compared are partly shaped by life in distinct ecological niches: human (and more largely hospital environment), louse, soil.
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