10 research outputs found

    SensibilitĂ© de champignons d'intĂ©rĂȘt mĂ©dical aux benzimidazolĂ©s (Ă©tude in vitro de l'action de l'albendazole (ZentelÂź) et du triclabendazole (EgatenÂź) par microdilution (NCCLS) et par microcalorimĂ©trie isotherme)

    No full text
    L'apparition de rĂ©sistance aux antifongiques nĂ©cessite de dĂ©couvrir de nouveaux agents susceptibles de lutter contre l'augmentation constante des infections opportunistes. Ce travail a consistĂ© en une Ă©tude de sensibilitĂ© in vitro selon les recommandations du NCCLS de champignons d'intĂ©rĂȘt mĂ©dical Ă  l'albendazole et au triclabendazole. L'Ă©tude effectuĂ©e par deux techniques diffĂ©rentes a confirmĂ© leurs activitĂ©s antifongiques envers les genres Candida spp. et Aspergillus spp., mais selon un spectre d'activitĂ© propre Ă  chacun. Le suivi de l'activitĂ© mĂ©tabolique par microcalorimĂ©trie isotherme nous a permis de mieux comprendre l'influence et l'action in vitro de ces molĂ©cules sur la croissance du champignon filamenteux. Des Ă©tudes complĂ©mentaires permettant de savoir si ces deux molĂ©cules peuvent Ă©ventuellement rejoindre l'arsenal thĂ©rapeutique destinĂ© Ă  lutter contre les infections fongiques.GRENOBLE1-BU MĂ©decine pharm. (385162101) / SudocSudocFranceF

    Pyrrolysine in archaea: a 22nd amino acid encoded through a genetic code expansion

    No full text
    International audienceThe 22nd amino acid discovered to be directly encoded, pyrrolysine, is specified by UAG. Until recently, pyrrolysine was only known to be present in archaea from a methanogenic lineage (Methanosarcinales), where it is important in enzymes catalysing anoxic methyla-mines metabolism, and a few anaerobic bacteria. Relatively new discoveries have revealed wider presence in archaea, deepened functional understanding, shown remarkable carbon source-dependent expression of expanded decoding and extended exploitation of the pyrrolysine machinery for synthetic code expansion. At the same time, other studies have shown the presence of pyrrolysine-containing archaea in the human gut and this has prompted health considerations. The article reviews our knowledge of this fascinating exception to the 'standard' genetic code

    The host-associated archaeome

    No full text
    International audienceHost-associated microbial communities have an important role in shaping the health and fitness of plants and animals. Most studies have focused on the bacterial, fungal or viral communities, but often the archaeal component has been neglected. The archaeal community, the so-called archaeome, is now increasingly recognized as an important component of host-associated microbiomes. It is composed of various lineages, including mainly Methanobacteriales and Methanomassiliicoccales (Euryarchaeota), as well as representatives of the Thaumarchaeota. Host–archaeome interactions have mostly been delineated from methanogenic archaea in the gastrointestinal tract, where they contribute to substantial methane production and are potentially also involved in disease-relevant processes. In this Review, we discuss the diversity and potential roles of the archaea associated with protists, plants and animals. We also present the current understanding of the archaeome in humans, the specific adaptations involved in interaction with the resident microbial community as well as with the host, and the roles of the archaeome in both health and disease

    Comparative genomics of microsporidian genomes reveals a minimal non-coding RNA set and new insights for transcription in minimal eukaryotic genomes

    No full text
    Microsporidia are ubiquitous intracellular pathogens whose opportunistic nature led to their increased recognition with the rise of the AIDS pandemic. As the RNA world was largely unexplored in this parasitic lineage, we developed a dedicated in silico methodology to carry out exhaustive identification of ncRNAs across the Encephalitozoon and Nosema genera. Thus, the previously missing U1 small nuclear RNA (snRNA) and small nucleolar RNAs (snoRNAs) targeting only the LSU rRNA were highlighted and were further validated using 5' and 3'RACE-PCR experiments. Overall, the 15 ncRNAs that were found shared between Encephalitozoon and Nosema spp. may represent the minimal core set required for parasitic life. Interestingly, the systematic presence of a CCC-or GGG-like motif in 5' of all ncRNA and mRNA gene transcripts regardless of the RNA polymerase involved suggests that the RNA polymerase machineries in microsporidia species could use common factors. Our data provide additional insights in accordance with the simplification processes observed in these reduce genomes and underline the usefulness of sequencing closely related species to help identify highly divergent ncRNAs in these parasites

    Colonic transit time is a driven force of the gut microbiota composition and metabolism: In vitro evidence

    No full text
    Jean-François BrugĂšre thanks bachelors’students for their help, more specifically CĂ©line Vidal, Claire Ardaens,Adeline RĂ©gnier, and Amandine Maurin, and Sylvain Denis forhis valuable help concerning in vitro systems. In memory of GeorgeT MacFarlane (died in 2015) for all of his pioneering works on gut in vitro simulations systemsThis work was supported by the European Union (UE) through the Auvergne Council (FEDER) with a PhD and a postdoctoral Scholarship support respectively to William Tottey and to David Feria-Gervasio, and by a PhD scholarship support from the French "Ministere de l'Enseignement Superieur et de la Recherche" to Nadia GaciBackground/Aims: Human gut microbiota harbors numerous metabolic properties essential for the host's health. Increased intestinal transit time affects a part of the population and is notably observed with human aging, which also corresponds to modifications of the gut microbiota. Thus we tested the metabolic and compositional changes of a human gut microbiota induced by an increased transit time simulated in vitro. Methods: The in vitro system, Environmental Control System for Intestinal Microbiota, was used to simulate the environmental conditions of 3 different anatomical parts of the human colon in a continuous process. The retention times of the chemostat conditions were established to correspond to a typical transit time of 48 hours next increased to 96 hours. The bacterial communities, short chain fatty acids and metabolite fingerprints were determined. Results: Increase of transit time resulted in a decrease of biomass and of diversity in the more distal compartments. Short chain fatty acid analyses and metabolite fingerprinting revealed increased activity corresponding to carbohydrate fermentation in the proximal compartments while protein fermentations were increased in the lower parts. Conclusions: This study provides the evidence that the increase of transit time, independently of other factors, affects the composition and metabolism of the gut microbiota. The transit time is one of the factors that explain some of the modifications seen in the gut microbiota of the elderly, as well as patients with slow transit time

    Phylogenomic Data Support a Seventh Order of Methylotrophic Methanogens and Provide Insights into the Evolution of Methanogenesis

    Get PDF
    International audienceIncreasing evidence from sequence data from various environments, including the human gut, suggests the existence of a previously unknown putative seventh order of methanogens. The first genomic data from members of this lineage, Methanomassiliicoccus luminyensis and " Candidatus Methanomethylophilus alvus, " provide insights into its evolutionary history and metabolic features. Phylogenetic analysis of ribosomal proteins robustly indicates a monophyletic group independent of any previously known metha-nogenic order, which shares ancestry with the Marine Benthic Group D, the Marine Group II, the DHVE2 group, and the Thermoplasmatales. This phylogenetic position, along with the analysis of enzymes involved in core methanogenesis, strengthens a single ancient origin of methanogenesis in the Euryarchaeota and indicates further multiple independent losses of this metabolism in nonmethanogenic lineages than previously suggested. Genomic analysis revealed an unprecedented loss of the genes coding for the first six steps of methanogenesis from H 2 /CO 2 and the oxidative part of methylotrophic methanogenesis, consistent with the fact that M. luminyensis and " Ca. M. alvus " are obligate H 2-dependent methylotrophic methanogens. Genomic data also suggest that these methanogens may use a large panel of methylated compounds. Phylogenetic analysis including homologs retrieved from environmental samples indicates that methylotrophic methanogenesis (regardless of dependency on H 2) is not restricted to gut representatives but may be an ancestral characteristic of the whole order, and possibly also of ancient origin in the Euryarchaeota. 16S rRNA and McrA trees show that this new order of methanogens is very diverse and occupies environments highly relevant for methane production, therefore representing a key lineage to fully understand the diversity and evolution of methanogenesis

    Three-stage continuous culture system with a self-generated anaerobia to study the regionalized metabolism of the human gut microbiota

    No full text
    This work was supported by a postdoctoral scholarship support from the European Union (UE) and the Auvergne Council, to D. F.-G. (FEDER), by a PhD Scholarship support from the European Union (UE) and the Auvergne Council to W.T. (FEDER), and to a PhD Scholarship support from the French "Ministere de l'Enseignement Superieur et de la Recherche". We thank Pascal Vandekerckove from Lesaffre SA and Zsolt Popse from Global Process Concept (France) for their support. J.-F.B. thanks Celine Vidal and Claire Ardaens for their technical help.The technical and ethical difficulties in studying the gut microbiota in vivo warrant the development and improvement of in vitro systems able to simulate and control the physicochemical factors of the gut biology. Moreover, the functional regionalization of this organ implies a model simulating these differences. Here we propose an improved and alternative three-stage continuous bioreactor called 3S-ECSIM (three-stage Environmental Control System for Intestinal Microbiota) to study the human large intestine. Its main feature compared with other in vitro systems is the anaerobic atmosphere originating directly from the microbiota metabolism, leading to different gas ratios of CO2 and H-2 in each compartment Analyses of the metabolic and microbiological profiles (LC-MS and a phylogenetic microarray) show different profiles together with a maintenance of this differentiation between the three compartments, simulating respectively a proximal, a transversal and a distal colon. Moreover, the last reactor presents a high similarity with the initial fecal sample, at the microbiological diversity level. Based on our results, this in-vitro process improvement is a valuable alternative tool to dynamically study the structure and metabolism of gut microbiota, and its response to nutrients, prebiotics, probiotics, drugs or xenobiotics. (C) 2013 Elsevier B.V. All rights reserved

    Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

    No full text
    International audienc
    corecore