Publications

PUBLICATIONS

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HAL : Dernières publications

  • [hal-04835060] Bioinspired 4D Printed Tubular/Helicoidal Shape Changing Metacomposites for Programmable Structural Morphing

    Abstract Biological structures combine passive shape‐changing with force generation through intricate composite architectures. Natural fibers, with their tubular‐like structures and responsive components, have inspired the design of pneumatic tubular soft composite actuators. However, no development of passive structural actuation is available despite the recent rise of 4D printing. In this study, a biomimicry approach is proposed with inspiration from natural fiber architecture to create a novel concept of thermally active 4D printed tubular metacomposites. These metacomposites exhibit high mechanical performance and 3D‐to‐3D shape‐changing ability triggered by changes in temperature. A rotative printer is proposed for winding a continuous carbon fibers reinforced PolyAmide 6.I composite on a PolyAmide 6.6 polymer mandrel in a similar manner to the structure of cellulose microfibrils within the polysaccharide matrix of natural fiber cell‐walls. The resulting 4D printed tubular metacomposites exhibit programmable rotation and torque in response to thermal variations thanks to the control of their mesostructure and the overall geometry. Energy density values representing a trade‐off between the rotation and the torque are comparable to shape memory alloys when normalized by stiffness. Finally, a proof of concept for an autonomous solar tracker is presented, showcasing its potential for designing autonomous assemblies for structure morphing.

    ano.nymous@ccsd.cnrs.fr.invalid (A. Le Duigou) 17 Dec 2024

    https://hal.science/hal-04835060v1
  • [inserm-04961151] Correlation Between Electronic Patient-Reported Outcomes and Biological Markers of Key Parameters in Acute Radiation Cystitis Among Patients With Prostate Cancer (RABBIO): Prospective Observational Study

    ackground: Despite advances in radiation techniques, radiation cystitis (RC) remains a significant cause of morbidity from pelvic radiotherapy, which may affect patients' quality of life (QoL). The pathophysiology of RC is not well understood, which limits the development of effective treatments. Objective: The Radiotoxicity Bladder Biomarkers study aims to investigate the correlation between blood and urinary biomarkers and the intensity of acute RC symptoms and QoL in patients undergoing localized prostate cancer radiotherapy. Methods: This study included patients with low- or intermediate-risk localized prostate cancer who were eligible for localized radiotherapy. Blood and urinary biomarkers were analyzed before radiotherapy was initiated and at weeks 4 and 12 of radiation therapy. Patients completed questionnaires related to RC symptoms and QoL (International Prostate Symptom Score and Functional Assessment of Cancer Therapy-Prostate [FACT-P]) using a digital remote monitoring platform. The information was processed by means of an algorithm, which classified patients according to the severity of symptoms and adverse events reported. Levels of blood and urinary biomarkers were tested with the severity of acute RC symptoms and patient-reported QoL. Results: A total of 401 adverse events questionnaires were collected over the duration of this study from 20 patients. The most frequently reported adverse events at week 4 were pollakiuria, constipation, and diarrhea. In comparison with baseline, the mean FACT-P score decreased at week 4. A significant increase in the proportion of M2 phenotype cells (CD206+, CD163+, CD204+) at W12 compared to W0 was observed. An increase in serum and urine levels of macrophage colony-stimulating factor (M-CSF), hepatocyte growth factor, and macrophagic inflammatory protein was observed at week 12 compared to baseline levels. Baseline serum and urine M-CSF concentrations showed a significant negative correlation with FACT-P scores at weeks 4 and 12 (r=-0.65, P=.04, and r=-0.76, P=.02, respectively). Conclusions: The Radiotoxicity Bladder Biomarkers study is the first to explore the overexpression of inflammatory proteins in blood and urine of patients with symptoms of acute RC. These preliminary findings suggest that serum and urine levels of hepatocyte growth factor, M-CSF, and macrophagic inflammatory protein, as well as macrophage polarization, are mobilized after prostate radiotherapy. The elevated M-CSF levels in serum and urine at baseline were associated with the deterioration of QoL during radiotherapy. The results of this study may help to develop mitigation strategies to limit radiation damage to the bladder.

    ano.nymous@ccsd.cnrs.fr.invalid (Carole Helissey) 21 Feb 2025

    https://inserm.hal.science/inserm-04961151v1
  • [hal-02941029] Sulfiredoxin Protects Mice from Lipopolysaccharide-Induced Endotoxic Shock

    Peroxiredoxins constitute a major family of cysteine-based peroxide-scavenging enzymes. They carry an intriguing redox switch by undergoing substrate-mediated inactivation via overoxidation of their catalytic cysteine to the sulfinic acid form that is reverted by reduction catalyzed by the sulfinic acid reductase sulfiredoxin (Srx). The biological significance of such inactivation is not understood, nor is the function of Srx1. To address this question, we generated a mouse line with a null deletion of the Srx1-encoding Srxn1 gene. We show here that Srxn1(-/-) mice are perfectly viable and do not suffer from any apparent defects under laboratory conditions, but have an abnormal response to lipopolysaccharide that manifests by increased mortality during endotoxic shock. Microarray-based mRNA profiles show that although the response of Srxn1(-/-) mice to lipopolysaccharide is typical, spanning all spectrum and all pathways of innate immunity, it is delayed by several hours and remains intense when the response of Srxn1(+/+) mice has already dissipated. These data indicate that Srx1 activity protects mice from the lethality of endotoxic shock, adding this enzyme to other host factors, as NRF2 and peroxiredoxin 2, which by regulating cellular reactive oxygen species levels act as important modifiers in the pathogenesis of sepsis.

    ano.nymous@ccsd.cnrs.fr.invalid (Anne-Gaëlle Planson) 16 Sep 2020

    https://hal.inrae.fr/hal-02941029v1
  • [tel-04148061] Biodiversité et fonctionnalités de la flore lactique autochtone des produits laitiers fermentés de chèvre au Liban

    Au Liban, la production de produits fermentés traditionnels à partir de lait cru de chèvre est réalisée par un petit nombre de producteurs, avec un vrai risque de disparition de ces produits et de perte de leur microflore. Cette thèse vise à étudier la biodiversité et les fonctionnalités des bactéries lactiques isolées des trois produits : Ambriss, Serdaleh et Labneh El Darff. 34 échantillons ont été collectés. Leur composition a été déterminée par des analyses culture-dépendantes et à l'aide d'outils métagénétiques et métagénomiques. Les résultats diffèrent selon les produits. Le Serdaleh révèle une codominance de L. kefiranofaciens et L. lactis qui se trouve dans un état viable mais non cultivable. Cette composition évoque celle des grains de kéfir, bien que L. kefiranofaciens se différencie par les gènes codant pour la production d'EPS. Les souches de L. lactis possèdent un plasmide portant des gènes de résistance aux antibiotiques. Le Labneh El Darff présente une dominance de L. delbrueckii, provenant probablement du Laban. Plusieurs pathogènes zoonotiques ont aussi été détectés. Les propriétés technologiques de 40 isolats ont été étudiées. L'activité acidifiante des entérocoques, lactocoques et des souches de L. rhamnosus et P. acidilactici est similaire, alors qu'elle est plus variable au sein des autres espèces. L'étude des propriétés physiques des laits fermentés montre que certaines souches conduisent à une forte fermeté (E. durans LD50, L. diolivorans LD47), tandis que d'autres génèrent des gels très cohésifs (L. paracasei LP12, L. kisonensis LKN28, L. brevis LB36, E. durans ED65). Une faible viscosité apparente a été observée pour tous les isolats. Le degré de synérèse varie beaucoup selon les espèces (faible chez L. diolivorans mais élevée chez L. plantarum). 17 composés d'arômes ont identifiés dans les cultures des souches: 6 acides gras volatils, 4 alcools, 3 cétones, 2 furanes, un composé carbonylé et un ester. Leur production diffère selon les souches, les isolats L. lactis LL01 et L. diolivorans LD46 générant les plus fortes quantités de composés d'arôme. Enfin, la plupart des isolats sont résistants au stress gastro-intestinal, les espèces L. kefiranofaciens et L. brevis étant les plus résistantes. Finalement, ces travaux ont permis de mettre en valeur les souches L. plantarum LP14 et LP15 pour être sélectionnées comme ferments pour la production de Serdaleh ou d'Ambriss, et les souches L. diolivorans LD44 et LD45 qui pourront être valorisées pour la fabrication de fromages de chèvre traditionnels Libanais.

    ano.nymous@ccsd.cnrs.fr.invalid (Imad Ammoun) 02 Jul 2023

    https://pastel.hal.science/tel-04148061v1
  • [tel-04416379] Analyse multiomique des peptides d’extraits de levure et de leurs impacts fonctionnels sur Streptococcus thermophilus

    Les bactéries lactiques sont largement utilisées en tant que ferments dans l'industrie laitière. Leur production s’effectue généralement dans des milieux semi-définis ou complexes dans lesquels certains nutriments peuvent être apportés par des extraits de levure (EXLs). Ce projet de thèse, qui associe deux partenaires industriels, les groupes Lesaffre et Sacco, ainsi que l’INRA, s’est focalisé sur l’effet des peptides de deux EXLs (EXL1 et EXL2) sur une souche industrielle de Streptococcus thermophilus, un levain lactique d’intérêt économique majeur. L’hypothèse sous-jacente était que ces peptides pourraient avoir un double rôle de nutrition et de régulation de fonctions cellulaires pouvant présenter un intérêt technologique. Afin d’explorer cette question, une stratégie expérimentale à deux niveaux a été élaborée : i) caractérisation et suivi cinétique de la fraction peptidique des deux EXLs par spectrométrie de masse (peptidomique) durant la fermentation de S. thermophilus en bioréacteurs, et ii) suivi cinétique parallèle du transcriptome et du protéome de la bactérie. L’objectif final était de croiser ces deux niveaux d’information afin de corréler des différences de contenu peptidique avec des différences d’activation de systèmes participant aux performances globales du levain.La caractérisation et le suivi du peptidome des EXLs en cours de fermentation a nécessité un important travail de développement méthodologique ayant abouti in fine à l’élaboration d’un outil analytique complet, combinant analyse peptidomique à haut-débit des échantillons et traitement bioinformatique et statistique des données. Cet outil a permis d’identifier environ 4000 peptides différents composant les deux EXLs. Le suivi cinétique a notamment permis de préciser la spécificité du transporteur d’oligopeptides de la bactérie (Ami). En particulier, il s’est avéré qu’une charge nette positive était le facteur prévalent pour le transport des peptides chez S. thermophilus. En complément de cette approche semi-quantitative, des analyses quantitatives ont été réalisées sur des fractions peptidiques des EXLs (dosages différentiels par HPLC des acides aminés avant et après hydrolyse). Elles ont notamment permis de révéler d’importantes différences de teneurs en oligopeptides entre les deux EXLs.En parallèle, le suivi transcriptomique et protéomique réalisé durant la croissance de la bactérie a révélé deux faits marquants. Le premier fait a trait à la surexpression dans l’EXL1 d’un locus génétique régulé par un mécanisme de quorum sensing utilisant un peptide phéromone comme signal moléculaire. Le deuxième fait marquant concerne diverses voies de biosynthèse (acides aminés et purines) différentiellement affectées par les deux EXLs. L’origine de ces dynamiques pourrait être au moins pour partie le fait de différences de contenu peptidique entre les deux substrats. Notamment, certaines voies de biosynthèse pourraient avoir été modulées différentiellement sous l’action de régulateurs centraux tels que CodY, dont l’activité est corrélée au contenu peptidique du milieu, ou encore YebC, un régulateur CodY-like dont le lien fonctionnel avec CodY reste encore inconnu chez S. thermophilus. Tous ces résultats ouvrent d’intéressantes perspectives pour mieux explorer le lien entre peptides et métabolisme bactérien. A terme, cette démarche pourrait se traduire par l’identification de biomarqueurs de performances dans les EXLs, et l’élaboration à façon de produits permettant de maximiser le potentiel technologique des ferments lactiques.

    ano.nymous@ccsd.cnrs.fr.invalid (Lucas Proust) 25 Jan 2024

    https://theses.hal.science/tel-04416379v1
  • [hal-01605182] Bovine and murine models highlight novel roles for SLC25A46 in mitochondrial dynamics and metabolism, with implications for human and animal health

    Neuropathies are neurodegenerative diseases affecting humans and other mammals. Many genetic causes have been identified so far, including mutations of genes encoding proteins involved in mitochondrial dynamics. Recently, the "Turning calves syndrome", a novel sensorimotor polyneuropathy was described in the French Rouge-des-Prés cattle breed. In the present study, we determined that this hereditary disease resulted from a single nucleotide substitution in SLC25A46, a gene encoding a protein of the mitochondrial carrier family. This mutation caused an apparent damaging amino-acid substitution. To better understand the function of this protein, we knocked out the Slc25a46 gene in a mouse model. This alteration affected not only the nervous system but also altered general metabolism, resulting in premature mortality. Based on optic microscopy examination, electron microscopy and on biochemical, metabolic and proteomic analyses, we showed that the Slc25a46 disruption caused a fusion/fission imbalance and an abnormal mitochondrial architecture that disturbed mitochondrial metabolism. These data extended the range of phenotypes associated with Slc25a46 dysfunction. Moreover, this Slc25a46 knock-out mouse model should be useful to further elucidate the role of SLC25A46 in mitochondrial dynamics.

    ano.nymous@ccsd.cnrs.fr.invalid (Amandine Duchesne) 26 May 2020

    https://hal.science/hal-01605182v1
  • [hal-04099006] A versatile active learning workflow for optimization of genetic and metabolic networks

    Abstract Optimization of biological networks is often limited by wet lab labor and cost, and the lack of convenient computational tools. Here, we describe METIS, a versatile active machine learning workflow with a simple online interface for the data-driven optimization of biological targets with minimal experiments. We demonstrate our workflow for various applications, including cell-free transcription and translation, genetic circuits, and a 27-variable synthetic CO 2 -fixation cycle (CETCH cycle), improving these systems between one and two orders of magnitude. For the CETCH cycle, we explore 10 25 conditions with only 1,000 experiments to yield the most efficient CO 2 -fixation cascade described to date. Beyond optimization, our workflow also quantifies the relative importance of individual factors to the performance of a system identifying unknown interactions and bottlenecks. Overall, our workflow opens the way for convenient optimization and prototyping of genetic and metabolic networks with customizable adjustments according to user experience, experimental setup, and laboratory facilities.

    ano.nymous@ccsd.cnrs.fr.invalid (Amir Pandi) 16 May 2023

    https://hal.inrae.fr/hal-04099006v1
  • [hal-02640520] Fine mapping and characterization of the L-polymerase-binding domain of the respiratory syncytial virus phosphoprotein

    The minimum requirement for an active RNA-dependent RNA polymerase of respiratory syncytial virus (RSV) is a complex made of two viral proteins, the polymerase large protein (L) and the phosphoprotein (P). Here we have investigated the domain on P that is responsible for this critical P-L interaction. By use of recombinant proteins and serial deletions, an L binding site was mapped in the C-terminal region of P, just upstream of the N-RNA binding site. The role of this molecular recognition element of about 30 amino acid residues in the L-P interaction and RNA polymerase activity was evaluated in cellula using an RSV mini-genome system and site-directed mutagenesis. The results highlighted the critical role of hydrophobic residues located in this region. IMPORTANCE Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants. Since no vaccine and no good antivirals against RSV are available, it is essential to better understand how the viral machinery functions in order to develop new antiviral strategies. Like all negative-strand RNA viruses, RSV codes for its own machinery to replicate and transcribe its genome. The core of this machinery is composed of two proteins, the phosphoprotein (P) and the large protein (L). Here, using recombinant proteins, we have mapped and characterized the P domain responsible for this L-P interaction and the formation of an active L-P complex. These findings extend our understanding of the mechanism of action of RSV RNA polymerase and allow us to define a new target for the development of drugs against RSV.

    ano.nymous@ccsd.cnrs.fr.invalid (Julien Sourimant) 28 May 2020

    https://hal.inrae.fr/hal-02640520v1
  • [hal-04871841] Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases

    Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse-transcytosis, the apical-to-basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan-glycan interaction. Here, we asked whether IgA1 and IgA2-microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLCpurified IgA, we show that reverse-transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA-bound microbiota in CD and UC showed distinct IgA1-and IgA2-associated microbiota; the IgA1 + fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti-glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.

    ano.nymous@ccsd.cnrs.fr.invalid (Eva Michaud) 07 Jan 2025

    https://hal.science/hal-04871841v1
  • [hal-02889105] Synthesis and antibacterial activity of iron manganite (FeMnO 3 ) particles against the environmental bacterium Bacillus subtilis †

    Nanocrystalline iron manganite powder was synthesized using the sol-gel combustion process, with glycine as fuel. It was further calcined at 900 C for 8 h, resulting in the formation of a loose cubic FeMnO 3 powder with a small specific surface area, net-like structure and plate-like particles as confirmed by XRD, N 2 physisorption, FESEM and TEM analyses. The metal ion release was studied by ICP-OES and showed that less than 10 ppb of Fe or Mn ions were released by leaching in water, but 0.36 ppm Fe and 3.69 ppm Mn was found in LB (Luria-Bertani) bacterial medium. The generation of reactive oxygen species (ROS) was monitored in distilled water and bacterial medium and showed that FeMnO 3 particles do not generate O 2 c À ions with or without UV irradiation, but synthesize H 2 O 2 and show an antioxidative effect. Besides the higher stability of FeMnO 3 particles in aqueous solution they showed an inhibitory effect on Bacillus subtilis growth in LB medium even at low concentrations (0.01 mg ml À1), but not in BHI medium even at 1 mg ml À1. This study points out that the mechanism of antibacterial action of engineered metal oxides needs continued investigation and specific experimental controls.

    ano.nymous@ccsd.cnrs.fr.invalid (Zorka Z Vasiljevic) 03 Jul 2020

    https://hal.inrae.fr/hal-02889105v1
  • [hal-01602539] Exploring complex transitions between polymorphs on a small scale by coupling AFM, FTIR and DSC: the case of Irganox 1076 (R) antioxidant

    This study illustrates the significant interest of using atomic force microscopy (AFM) in force curve imaging mode for discovering and studying not easily detectable solid/solid transitions between polymorphs: we show that AFM in this imaging mode is a powerful means for studying in situ these transitions as they can be (i) detected in a very early step because of the high spatial resolution (at nanometer scale) of AFM and (ii) be distinguished from melting/recrystallization processes that can occur in the same temperature range. This was illustrated with the case of Irganox 1076 (R). This compound is a phenolic antioxidant currently used in standard polymers; it can bloom on the surface of polymer-based medical devices and its polymorphism might affect the device surface state and thus the biocompatibility. In a previous paper, the polymorphism of this compound was studied: four forms were characterized at a macroscopic level and one of them (form III) was identified on the surface of a polyurethane catheter. However, it was difficult to characterize the transitions between the different forms with only classical tools (DSC, FTIR and SAXS). In the present study, to evidence these transitions, we use AFM measurements coupled with a heating stage and we correlate them to ATR-FTIR measurements and to DSC analysis. This new study put into evidence a solid-solid transition between form III and II.

    ano.nymous@ccsd.cnrs.fr.invalid (Johanna Saunier) 26 May 2020

    https://hal.science/hal-01602539v1
  • [hal-05046362] DNA repair | Nonhomologous End-Joining in Bacteria

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    ano.nymous@ccsd.cnrs.fr.invalid (Annabelle Thibessard) 25 Apr 2025

    https://hal.inrae.fr/hal-05046362v1
  • [inserm-05026556] Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19

    Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.

    ano.nymous@ccsd.cnrs.fr.invalid (Patrícia Brito Rodrigues) 09 Apr 2025

    https://inserm.hal.science/inserm-05026556v1
  • [anses-04171498] Avis de l'Anses relatif à la définition des souches pathogènes d’Escherichia coli productrices de shigatoxines

    Les Escherichia coli entérohémorragiques (EHEC) sont des souches pathogènes d’E. coli responsables de diarrhée ou de colite hémorragique pouvant s’aggraver en syndrome hémolytique et urémique (SHU), surtout chez le jeune enfant, le sujet âgé et/ou immunodéprimé. L’avis de l’Anses du 18 mai 2017 indique que toute souche d’E. coli isolée chez l’Homme ou dans les aliments devrait être considérée comme une EHEC si elle possède les gènes de virulence stx1 et/ou stx2 et eae ou d’autre(s) gène(s) codant un système d’adhésion au tube digestif de l’Homme (Anses 2017). Certains sérotypes d’EHEC sont plus fréquemment associés à une maladie grave (SHU). L’Agence avait établi dans cet avis une classification des souches en fonction de leur risque pour la santé publique en France, selon les critères définis par le panel BIOHAZ de l’EFSA en 2013 (sérotypes et facteurs de virulence) et en se fondant sur les données épidémiologiques françaises et européennes. En 2018, un groupe d’experts FAO/OMS a proposé un ensemble de critères pour catégoriser les souches d’E. coli productrices de shigatoxines (STEC) en fonction du risque de forme clinique sévère (FAO/WHO 2018). Cinq niveaux de risque sont définis sur la base des profils de gènes de virulence. Le groupe conclut que le sérotype ne devrait pas être considéré comme un critère pour prédire la virulence des souches. En janvier 2020, l'EFSA a publié l’avis du panel BIOHAZ concernant l’évaluation de la pathogénicité des STEC sur la base des données de santé publique disponibles en Europe (EFSA BIOHAZ Panel 2020). Cet avis conclut que toutes les souches de STEC sont pathogènes avec la capacité de causer a minima une diarrhée, et que tous les sous-types de STEC peuvent être associés à des maladies sévères chez l’Homme. Le panel BIOHAZ de l’EFSA considère que la classification de la pathogénicité des STEC en fonction des sérotypes et de la présence de facteurs de virulence proposée dans son précédent avis de 2013 n’est plus valide. L’Anses est saisie pour actualiser voire compléter la définition des souches pathogènes proposée dans l'avis de mai 2017 au vu de l'avis du panel BIOHAZ de l'EFSA (2020), du rapport FAO/OMS (2018) et des autres données et publications récentes qui pourraient alimenter la réflexion. Les questions posées dans la saisine sont les suivantes : - « Sur la base des données de santé publique disponibles, quels sont les déterminants de la virulence des souches de STEC ? - Dans quelle mesure la prise en compte des sous-types du gène stx ou de tout autre facteur génétique permettrait-elle de rendre plus discriminante la typologie des souches de STEC proposée dans votre avis de mai 2017 au regard de leur niveau de pathogénicité ? »

    ano.nymous@ccsd.cnrs.fr.invalid (Philippe Fravalo) 26 Jul 2023

    https://anses.hal.science/anses-04171498v1
  • [anses-04854468] Avis de l’Anses relatif à l’évaluation du risque de transmission du complexe Mycobacterium tuberculosis à l'humain via la consommation de produits laitiers crus issus d’un élevage caprin infecté

    La tuberculose bovine à déclaration obligatoire est provoquée par les bactéries du complexe Mycobacterium tuberculosis : M. bovis, M. caprae et M. tuberculosis. Cependant, en France, le seul agent pathogène impliqué dans des cas autochtones de tuberculose animale est M. bovis. La tuberculose à M. bovis constitue un problème sanitaire majeur de l’élevage notamment bovin et porcin en Corse. Les foyers bovins en Corse représentent 20 % des foyers bovins de tuberculose de France hexagonale. La tuberculose à M. bovis y est également présente au sein de la faune sauvage, notamment chez les sangliers et chez les bovins féraux, constituant ainsi un système multi-hôtes complexe où l’environnement et la faune sauvage pourraient constituer une source de recontamination des troupeaux. C’est dans ce contexte qu’un foyer de tuberculose à M. bovis a été détecté dans un atelier caprin en lien épidémiologique avec un foyer bovin, dans le Cap-Corse, en avril 2023, constituant le premier foyer dans un cheptel caprin en Corse depuis 2009. L’élevage caprin en race Corse est un système d’élevage pastoral, où le lait sert quasi-exclusivement à la fabrication de fromage au lait cru, très majoritairement fabriqué à la ferme.

    ano.nymous@ccsd.cnrs.fr.invalid (Georges Daube) 23 Jan 2025

    https://anses.hal.science/anses-04854468v1
  • [anses-04350896] Avis de l'Anses relatif à la présence de parasites Toxocara spp. dans les viandes de sanglier sauvage

    Des analyses sur les carcasses de sangliers sauvages inspectées dans les établissements français de traitement de gibiers sauvages ont révélé depuis deux ans la présence régulière de larves de Toxocara spp. Ce constat a conduit les services vétérinaires d'inspection à saisir ces carcasses, conformément à l'article 45 du règlement d'exécution (UE) n°2019/627 de la Commission du 15 mars 2019 qui prévoit que les viandes présentant une infestation parasitaire sont déclarées impropres à la consommation humaine. La problématique pour le gestionnaire est double. Le premier enjeu est lié au risque de toxocarose pour les consommateurs de viandes de sanglier et des recommandations relatives à la conservation et la cuisson des viandes à adresser aux chasseurs. Le second enjeu est relatif à la gestion des lots de sangliers détectés positifs. Les demandes instruites dans le cadre de cette expertise sont les suivantes : Demande 1 : Établir un profil de risque pour Toxocara spp. dans les viandes de sanglier sauvage. Demande 2 : Évaluer l’efficacité de traitements assainissants de la carcasse sur la viabilité du parasite Toxocara spp., plus particulièrement la congélation et la cuisson, dans le cas où ces traitements sont réalisés, soit par les établissements du secteur alimentaire, soit directement par les consommateurs.

    ano.nymous@ccsd.cnrs.fr.invalid (Philippe Fravalo) 12 Mar 2024

    https://anses.hal.science/anses-04350896v1
  • [hal-04994246] Diet, fruit and vegetables and One Health: benefits for health, environment, society and the consumer—proceedings of the 9th edition of EGEA conference

    Purpose To present the outcomes of the EGEA Conference on the state of knowledge regarding the contribution of diets rich in fruit and vegetables (FV) to human and planetary health, commonly included in the One Health concept. Methods The 9th edition of EGEA Conference (20-22 September 2023, Barcelona) provided a transversal and multidisciplinary perspective on the contribution of FV to One Health, in particular to the health of individuals, society and the planet. Nearly 150 international scientists and stakeholders discussed the current state of knowledge. These proceedings are based both on a literature review and the scientic studies presented by the speakers. Results Scientic evidence conrms the role of FV in preventing cardiovascular diseases and type 2 diabetes; more evidence is needed on the eects and mechanisms of FV in cancer prevention. FV production and consumption helps ensure territorial cohesion and provides a denser, nutrient-rich diet with less environmental impact (except water use) than other food groups, but use of synthetic pesticides in FV production remains a challenge that could be addressed with agro-ecological solutions. Various factors inuence consumer choice and behaviour towards FV consumption across the lifespan, with specic periods being more conducive to change. New research is emerging on the role of FV consumption in regulating gut microbiota and on both mental and brain health; the potential role of FV production and supply in tackling biodiversity loss and climate change; and better monitoring of FV consumption. Conclusion Sucient evidence conrms the contribution of diet rich in FV to One Health, with some emerging research on this topic. Concerted actions are required towards an increased consumption of FV and a more diversied and environmentally neutral FV production.

    ano.nymous@ccsd.cnrs.fr.invalid (Nathalie Komati) 17 Mar 2025

    https://hal.inrae.fr/hal-04994246v1
  • [hal-04453098] Identification of a muropeptide precursor transporter from gut microbiota and its role in preventing intestinal inflammation

    The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes. Extensive purification of the clone’s supernatant demonstrates that the ABC-transporter allows for the efficient extracellular accumulation of three muropeptide precursor, with anti-inflammatory properties. They induce IL-10 secretion from human monocyte-derived dendritic cells and proved effective in reducing AIEC LF82 epithelial damage and IL-8 secretion in human intestinal resections. In addition, treatment with supernatants containing the muropeptide precursor reduces body weight loss and improves histological parameters in Dextran Sulfate Sodium (DSS)-treated mice. Until now, the source of peptidoglycan fragments was shown to come from the natural turnover of the peptidoglycan layer by endogenous peptidoglycan hydrolases. This is a report showing an ABC-transporter as a natural source of secreted muropeptide precursor and as an indirect player in epithelial barrier strengthening. The mechanism described here might represent an important component of the host immune homeostasis.

    ano.nymous@ccsd.cnrs.fr.invalid (Sophie Liuu) 12 Feb 2024

    https://amu.hal.science/hal-04453098v1
  • [hal-03352896] Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease

    Background An Escherichia coli (E. coli) pathotype with invasive properties, first reported by Darfeuille-Michaud and termed adherent-invasive E. coli (AIEC), was shown to be prevalent in up to half the individuals with Crohn’s Disease (CD), suggesting that these bacteria could be involved in the pathophysiology of CD. Among the genes related to AIEC pathogenicity, fim has the potential to generate an inflammatory reaction from the intestinal epithelial cells and macrophages, as it interacts with TLR4, inducing the production of inflammatory cytokines independently of LPS. Therefore, targeting the bacterial adhesion of FimH-expressing bacteria seems a promising therapeutic approach, consisting of disarming bacteria without killing them, representing a selective strategy to suppress a potentially critical trigger of intestinal inflammation, without disturbing the intestinal microbiota. Results We analyzed the metagenomic composition of the gut microbiome of 358 patients with CD from two different cohorts and characterized the presence of FimH-expressing bacteria. To assess the pathogenic role of FimH, we used human intestinal explants and tested a specific FimH blocker to prevent bacterial adhesion and associated inflammation. We observed a significant and disease activity-dependent enrichment of Enterobacteriaceae in the gut microbiome of patients with CD. Bacterial FimH expression was functionally confirmed in ileal biopsies from 65% of the patients with CD. Using human intestinal explants, we further show that FimH is essential for adhesion and to trigger inflammation. Finally, a specific FimH-blocker, TAK-018, inhibits bacterial adhesion to the intestinal epithelium and prevents inflammation, thus preserving mucosal integrity. Conclusions We propose that TAK-018, which is safe and well tolerated in humans, is a promising candidate for the treatment of CD and in particular in preventing its recurrence.

    ano.nymous@ccsd.cnrs.fr.invalid (Grégoire Chevalier) 23 Sep 2021

    https://hal.sorbonne-universite.fr/hal-03352896v1
  • [hal-05019485] Maximization of production in cell-free systems using active learning - Dr. Olivier Borkowski

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Olivier Borkowski) 03 Apr 2025

    https://hal.science/hal-05019485v1
  • [hal-04792054] Prophages divert Staphylococcus aureus defenses against host lipids

    Phages are ubiquitous in bacteria, including clinical Staphylococcus aureus, where Sfi 21/Sa3 phages often integrate into the hlb gene, which encodes Hlb sphingomyelinase. This integration acts as a rapid regulatory switch for Hlb production. Our findings suggest that Sfi 21/Sa3 prophages and Hlb activity influence S. aureus fitness by modulating the incorporation of the toxic linoleic acid (C18:2) from serum into the bacterial membrane. This process relies on C18:2 derived from 1,3-diglyceride, facilitated by the FakB1 kinase subunit. Palmitic acid (C16), primarily released from serum through Hlb activity, competes with C18:2 for FakB1. This mechanism contributes to adaptation to AFN-1252, an antibiotic inhibiting the fatty acid synthesis pathway (anti-FASII). Since S. aureus relies on exogenous fatty acids for growth, AFN-1252 treatment leads to increased proportion of C18:2 in the membrane. Furthermore, Hlb inhibition, whether by prophage insertion, gene inactivation, or enzyme inhibition, delays S. aureus adaptation, resulting in a higher proportion of C18:2 in the membrane. This study sheds light on the role of lipid environments in infections and may contribute to the accurate prediction of infection risks and therapeutic efficacy. Moreover, since both anti-FASII agent and Hlb inhibitor enhance C18:2 incorporation, they represent potential candidates for combined strategies against S. aureus.

    ano.nymous@ccsd.cnrs.fr.invalid (Biyang Zhou) 20 Nov 2024

    https://hal.science/hal-04792054v2
  • [hal-02044826] Bacterial NHEJ: A never ending story

    Double-strand breaks (DSBs) are the most detrimental DNA damage encountered by bacterial cells. DBSs can be repaired by homologous recombination thanks to the availability of an intact DNA template or by Non-Homologous End Joining (NHEJ) when no intact template is available. Bacterial NHEJ is performed by sets of proteins of growing complexity from Bacillus subtilis and Mycobacterium tuberculosis to Streptomyces and Sinorhizobium meliloti. Here, we discuss the contribution of these models to the understanding of the bacterial NHEJ repair mechanism as well as the involvement of NHEJ partners in other DNA repair pathways. The importance of NHEJ and of its complexity is discussed in the perspective of regulation through the biological cycle of the bacteria and in response to environmental stimuli. Finally, we consider the role of NHEJ in genome evolution, notably in horizontal gene transfer.

    ano.nymous@ccsd.cnrs.fr.invalid (Claire Bertrand) 21 Feb 2019

    https://hal.univ-lorraine.fr/hal-02044826v1
  • [hal-03151225] Tyrosine Nitration of Flagellins: a Response of Sinorhizobium meliloti to Nitrosative Stress

    Rhizobia are bacteria which can either live as free organisms in the soil or interact with plants of the legume family with, as a result, the formation of root organs called nodules in which differentiated endosymbiotic bacteria fix atmospheric nitrogen to the plant's benefit. In both lifestyles, rhizobia are exposed to nitric oxide (NO) which can be perceived as a signaling or toxic molecule. NO can act at the transcriptional level but can also modify proteins by S-nitrosylation of cysteine or nitration of tyrosine residues. However, only a few molecular targets of NO have been described in bacteria and none of them have been characterized in rhizobia. Here, we examined tyrosine nitration of Sinorhizobium meliloti proteins induced by NO. We found three tyrosine-nitrated proteins in S. meliloti grown under free-living conditions, in response to an NO donor. Two nitroproteins were identified by mass spectrometry and correspond to flagellins A and B. We showed that one of the nitratable tyrosines is essential to flagellin function in motility. IMPORTANCE Rhizobia are found as free-living bacteria in the soil or in interaction with plants and are exposed to nitric oxide (NO) in both environments. NO is known to have many effects on animals, plants, and bacteria where only a few molecular targets of NO have been described so far. We identified flagellin A and B by mass spectrometry as tyrosine-nitrated proteins in Sinorhizobium meliloti in vivo. We also showed that one of the nitratable tyrosines is essential to flagellin function in motility. The results enhanced our understanding of NO effects on rhizobia. Identification of bacterial flagellin nitration opens a new possible role of NO in plant-microbe interactions.

    ano.nymous@ccsd.cnrs.fr.invalid (Anne-Claire Cazalé) 24 Feb 2021

    https://hal.inrae.fr/hal-03151225v1
  • [hal-01607278] Siropins, novel serine protease inhibitors from gut microbiota acting on human proteases involved in inflammatory bowel diseases

    Background: In eukaryotes, the serpins constitute a wide family of protease inhibitors regulating many physiological pathways. Many reports stressed the key role of serpins in several human physiopathologies including mainly the inflammatory bowel diseases. In this context, eukaryotic serpins were largely studied and their use to limit inflammation was reported. In comparison to that, bacterial serpins and mainly those from human gut microbiota remain poorly studied. Results: The two genes encoding for putative serpins from the human gut bacterium Eubacterium sireaum, display low sequence identities. These genes were overexpressed and the encoded proteins, named Siropins, were purified. Activity studies demonstrated that both purified proteins inhibited serine proteases but surprisingly they preferentially inhibited two human serine proteases (Human Neutrophil Elastase and Proteinase3). The biochemical characterization of these Siropins revealed that Siropin 1 was the most active and stable at low pH values while Siropin 2 was more thermoactive and thermostable. Kinetic analysis allowed the determination of the stoichiometry of inhibition (SI) which was around 1 and of the association rate constants of 7.7 x 10(4) for the Human Neutrophil Elastase and 2.6 x 10(5) for the Proteinase3. Moreover, both Siropins displayed the ability to inhibit proteases usually present in fecal waters. Altogether our data indicate the high efficiency of Siropins and their probable involvement in the control of the overall intestine protease activity. Conclusions: Here we report the purification and the biochemical characterization of two novel serpins originated from Eubacterium sireaum, a human gastro-intestinal tract commensal bacteria. These proteins that we called Siropins, efficiently inhibited two human proteases reported to be associated with inflammatory bowel diseases. The determination of the biochemical properties of these enzymes revealed different temperature and pH behaviours that may reflect adaptation of this human commensal bacterium to different ecological environments. To the best of our knowledge, it is the first bacterial serpins showing an attractive inhibition of fecal proteases recovered from a mice group with chemically induced inflammation. Altogether our data highlight the interesting potential of Siropins, and serpins from the human gut microbiota in general, to be used as new alternative to face inflammatory diseases.

    ano.nymous@ccsd.cnrs.fr.invalid (Hela Mkaouar) 28 May 2020

    https://hal.science/hal-01607278v1
  • [hal-04879243] Responses to and detoxification of esculin in white-rot fungi

    Bio-based molecules have become one of the main alternatives to traditional products for limiting the spread of harmful fungi. However, a better understanding of the mode of action of these molecules and the defense systems developed by fungi to resist them, is needed to assess the benefits/risks of using them as antifungal treatment. White-rot fungi are excellent models in this respect, as they have adapted to the hostile habitat that is wood. In fact, wood is a source of putative antifungal compounds known as extractives. In this study, we demonstrated that esculin and the aglycone form esculetin, which are coumarins found in plants and wood, reduce the growth of Phanerochaete chrysosporium, Pycnoporus cinnabarinus, Trametes versicolor and Fomitiporia mediterranea, with some differences depending on the specie. We have shown that various strategies are developed by the fungi to deal with esculin both at the extracellular level, through the involvement of laccases, peroxidases and glycoside hydrolases, and at the intracellular level, mainly by stimulating protein translation. Using comparative proteomic and metabolomic approaches, our results showed that despite the fact that the species analyzed are closely related (they all belong to the Agaricomycotina, and have the same trophic mode), their defense responses to esculin are different.

    ano.nymous@ccsd.cnrs.fr.invalid (Raphael Bchini) 30 Jan 2025

    https://hal.inrae.fr/hal-04879243v1
  • [hal-04966675] Diversité de la levure Debaryomyces hansenii révélée à l’aide de pseudo-marqueurs microsatellite

    Le typage des souches est une démarche essentielle pour la sélection, le contrôle ou l’étude de la diversité des levures. Cette diversité a été explorée pour de nombreuses espèces de levures à l’aide d’empreintes moléculaires peu résolutives et peu robustes. Depuis 20 ans des marqueurs microsatellites ont été utilisés avec succès pour la caractérisation de souches de quelques espèces de levures comme Saccharomyces cerevisiae ou Torulaspora delbrueckii. Alors que l’espèce de levure Debaryomyces hansenii est rencontrée dans de nombreux environnements comme l’eau de mer, les fromages ou le vin ; il n’existe pas d’étude de diversité menée à l’aide de marqueurs génétiques robustes. Nous présentons ici un set de 15 marqueurs microsatellite pour la caractérisation de la diversité des levures Debaryomyces hansenii. Ce set de marqueurs nous permet de proposer une première vision de la structure de population chez cette espèce de levure.

    ano.nymous@ccsd.cnrs.fr.invalid (Cécile Grondin) 26 Feb 2025

    https://hal.inrae.fr/hal-04966675v1
  • [hal-03904120] Exploring the Diversity of Biofilm Formation by the Food Spoiler Brochothrix thermosphacta

    Brochothrix thermosphacta is considered as a major spoiler of meat and seafood products. This study explores the biofilm formation ability and the biofilm structural diversity of 30 multi-origin B. thermosphacta strains using a set of complementary biofilm assays (biofilm ring test, crystal violet staining, and confocal laser scanning microscopy). Two major groups corresponding to low and high biofilm producers were identified. High biofilm producers presented flat architectures characterized by high surface coverage, high cell biovolume, and high surface area.

    ano.nymous@ccsd.cnrs.fr.invalid (Antoine Gaillac) 03 Jan 2023

    https://hal.inrae.fr/hal-03904120v1
  • [hal-03664919] Human CD4+/CD8α+ regulatory T cells induced by Faecalibacterium prausnitzii protect against intestinal inflammation

    Faecalibacterium prausnitzii (F. prausnitzii), a dominant bacterium of the human microbiota, is decreased in patients with inflammatory bowel diseases (IBD) and exhibits anti-inflammatory effects. In human, colonic lamina propria contains IL-10-secreting, Foxp3-negative regulatory T cells (Treg) characterized by a double expression of CD4 and CD8α (DP8α) and a specificity for F. prausnitzii. This Treg subset is decreased in IBD. The in vivo effect of DP8α cells has not been evaluated yet. Here, using a humanized model of NOD.Prkcscid IL2rγ-/- (NSG) immunodeficient mouse strain that expresses the human leucocyte antigen D-related allele HLA-DR*0401 but not murine class II (NSG-Ab° DR4) molecules, we demonstrated a protective effect of a HLA-DR*0401-restricted DP8α Treg clone combined with F. prausnitzii administration in a colitis model. In a cohort of patients with IBD, we showed an independent association between the frequency of circulating DP8α cells and disease activity. Finally, we pointed out a positive correlation between F. prausnitzii-specific DP8α Tregs and the amount of F. prausnitzii in fecal microbiota in healthy individuals and patients with ileal Crohn's disease.

    ano.nymous@ccsd.cnrs.fr.invalid (Sothea Touch) 05 Dec 2023

    https://hal.science/hal-03664919v1
  • [pasteur-01977322] Minimum Information about an Uncultivated Virus Genome (MIUViG)

    We present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative studies and a systematic exploration of the global virosphere.

    ano.nymous@ccsd.cnrs.fr.invalid (Simon Roux) 10 Jan 2019

    https://pasteur.hal.science/pasteur-01977322v1
  • [hal-05040579] Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: Systematic Review and Meta-Analysis

    BACKGROUND: Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis were performed to compare the efficacy of single-donor (SDN) and multi-donor (MDN) strategies for product preparation. METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 non-randomized). The treatment response was assessed by using fixed and random effects models and the significance of the indirect difference between the interventions was assessed using a network approach. RESULTS: Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios (RRs): 4.41 and 1.57, respectively ( P ≤0.001 for both)), and MDN was superior to SDN (RR: 2.81, P =0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P =0.042). Results were identical for both models. CONCLUSIONS: There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.

    ano.nymous@ccsd.cnrs.fr.invalid (Benoît Levast) 19 Apr 2025

    https://hal.science/hal-05040579v1
  • [tel-05042813] Étude de la kurstakine et de Spo0A, deux facteurs d’adaptation de Bacillus thuringiensis

    Bacillus thuringiensis est une bactérie entomopathogène du groupe Bacillus cereus. En plus de sa capacité à infecter et tuer les larves d’insectes sensibles, B. thuringiensis peut survivre à l’état végétatif plus d’une semaine dans le cadavre de l’hôte qu’il vient de tuer ; un mode de développement appelé nécrotrophisme. Comme d’autres Bacillus, B. thuringiensis possède aussi plusieurs mécanismes d’adaptation : formation de biofilm, sporulation et synthèse de métabolites secondaires originaux, par exemple. Ceux-ci sont finement régulés en fonction de l’environnement, via des systèmes d’intégration de signaux extra-cellulaires qui convergent souvent vers des régulateurs transcriptionnels centraux, parmi lesquels Spo0A et NprR. Spo0A est notamment présent chez les espèces Bacillus et Clostridium, et contrôle un grand nombre de mécanismes d’adaptation. NprR est un régulateur de quorum sensing présent uniquement dans le groupe Bacillus cereus. Chez B. thuringiensis, lorsque le quorum est atteint, il permet la transition d’un mode de vie pathogène à nécrotrophe. Le travail mené au cours de cette thèse a eu pour but de mieux comprendre le comportement de B. thuringiensis en phase stationnaire et au cours de l’infection d’un insecte hôte.NprR régule la transcription d’une quarantaine de gènes, parmi lesquels le locus krs. Ce grand locus de 30 kb porte six gènes impliqués dans la synthèse non-ribosomique de la kurstakine, un lipo-heptapeptide susceptible de jouer un ou des rôle(s) importants dans le nécrotrophisme et revêtant un potentiel intérêt biotechnologique. Nous avons montré que les gènes sont co-transcrits à partir d’un promoteur en amont du premier gène, formant donc un opéron. La mesure de l’activité de ce promoteur nous a permis de mettre en évidence que celle-ci est fortement dépendante des conditions de croissance, et que sa régulation est complexe et fait intervenir, en plus de NprR, Spo0A et une séquence d’ADN palindromique dont la fonction est encore inconnue. Nous démontrons aussi que le produit de ce locus, la kurstakine, est impliqué dans la structuration du biofilm de B. thuringiensis.Dans le cadre d’une approche plus globale, nous avons caractérisé les transcriptomes de B. thuringiensis in vitro, à deux points dans le temps, et in vivo, dans la souche modèle 407 et le mutant de délétion de spo0A, en utilisant la technique de RNA-seq. Couplées à une prédiction in silico des boîtes Spo0A dans le génome de B. thuringiensis, ces données décrivent pour la première fois le régulon Spo0A d’une bactérie du groupe Bacillus cereus. Nous tentons également d’élucider le rôle de Spo0A dans le cycle infectieux de B. thuringiensis, et montrons que sans spo0A, B. thuringiensis est incapable de persister dans le cadavre de son hôte. Ce défaut de survie est indépendant de la sporulation, car un mutant affecté dans les étapes plus tardives de la sporulation survit. Cela suggère qu’une partie du régulon Spo0A est également impliquée dans mode de vie nécrotrophe de B. thuringiensis.

    ano.nymous@ccsd.cnrs.fr.invalid (Sébastien Gélis-Jeanvoine) 22 Apr 2025

    https://pastel.hal.science/tel-05042813v1
  • [hal-04316567] Contribution of the anaerobic blood culture vial for the recovery of Candida glabrata : A retrospective multicentric study

    Abstract Although Candida spp are aerobic microorganisms, some Candida strains, mainly Candida glabrata, can be recovered from anaerobic blood culture vials. We assessed the contribution of the anaerobic vials for the diagnosis of candidemia, especially for C. glabrata. We conducted a multicenter retrospective study including eight university or regional hospitals. A single episode of monomicrobial candidemia per patient was included from September 1st, 2016, to August 31st, 2019. The characteristics of all aerobic and anaerobic blood culture vials sampled within 2 h before and after the first positive blood culture vials were recorded (type of vials, result, and for positive vials time-to-positivity and Candida species). Overall, 509 episodes of candidemia were included. The main species were C. albicans (55.6%) followed by C. glabrata (17.1%), C. parapsilosis (4.9%), and C. tropicalis (4.5%). An anaerobic vial was positive in 76 (14.9%) of all episodes of which 56 (73.8%) were due to C. glabrata. The number of C. glabrata infections only positive in anaerobic vials was 1 (2.6%), 1 (11.1%), and 15 (37.5%) with the BACT/ALERT 3D the BACT/ALERT VIRTUO and the BACTEC FX instrument, respectively (P < 0.01). The initial positivity of an anaerobic vial was highly predictive of the isolation of C. glabrata with the BACTEC FX (sensitivity of 96.8%). C. glabrata time-to-positivity was shorter in anaerobic vial than aerobic vial with all instruments. Anaerobic blood culture vials improve the recovery of Candida spp mainly C. glabrata. This study could be completed by further analyses including mycological and pediatric vials. Lay summary Although Candida spp are aerobic microorganisms, C. glabrata is able to grow in anaerobic conditions. In blood culture, the time-to-positivity of C. glabrata is shorter in anaerobic than aerobic vials. Only the anaerobic vial was positive in up to 15 (37.5%) C. glabrata bloodstream infections.

    ano.nymous@ccsd.cnrs.fr.invalid (Eric Farfour) 30 Nov 2023

    https://hal.science/hal-04316567v1
  • [hal-04565273] New Approaches to Manage Infections in Transplant Recipients: Report From the 2023 GTI (Infection and Transplantation Group) Annual Meeting

    This year’s GTI (“Groupe Transplantation and Infection”) annual meeting was held in Paris, France in February 2023. This meeting focused on new approaches to manage infectious complications in solid organ and stem cell transplant recipients. In this meeting report, we summarize the presentations and discussions from this annual meeting. Covered topics included new anti-infective agents and non-antibiotic approaches to manage infections due to multidrug-resistant Gram-negative bacteria, staphylococci, and fungal infections, as well as new approaches to manage symptomatic urinary tract infections and asymptomatic bacteriuria in kidney transplant recipients. Innovative approaches are needed to manage infectious complications in transplant recipients, who are at high risk of difficult-to-treat infections and side effects associated with the use of anti-infective agents.

    ano.nymous@ccsd.cnrs.fr.invalid (Alexandra Serris) 17 Apr 2025

    https://hal.inrae.fr/hal-04565273v1
  • [hal-04707072] State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus

    Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts’ confidence in the potential of microbiomebased biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.

    ano.nymous@ccsd.cnrs.fr.invalid (Julie Rodriguez) 24 Sep 2024

    https://hal.inrae.fr/hal-04707072v1
  • [hal-04993522] Strain-dependent emergence of aminoglycoside resistance in Escherichia coli biofilms

    In most Earth environments, bacteria predominantly exist within surface-associated communities known as biofilms, where they are embedded in an extracellular matrix. These collective structures play a critical role in bacterial physiology and significantly shape their evolutionary trajectories, contributing to the development of antimicrobial resistance and enhancing bacterial resilience to treatments, with profound implications for public health. This study assessed the impact of the biofilm lifestyle on the emergence of resistance to gentamicin, an aminoglycoside antibiotic, in one laboratory reference strain and seven Escherichia coli isolates from foodprocessing environments. Throughout a one-month evolution experiment, we observed that certain strains showed a markedly higher emergence of gentamicin-resistant variants in biofilms than in planktonic states, with the emergence of stable variants being closely linked to biofilm maturation. Genomic and phenotypic analyses of gentamicin-resistant (GenR) variants uncovered varied adaptive strategies among the strains. GenR variants from two food-processing isolates (Ec709 and Ec478) displayed point mutations in genes associated with central carbon metabolism (aceE, ygfZ, …) and cell respiration (atpG, cydA, …), while retaining relative growth and colonization capacities. Conversely, GenR variants from the reference strain (Ec1655) adapted preferentially through large genomic deletions, including consistent loss of the peptide transporter gene sbmA, significantly altering cellular fitness. These findings highlight the complexity of adaptive evolution in biofilms and underscore the importance of investigating diverse strains to grasp the full spectrum of adaptation in natural bacterial populations.

    ano.nymous@ccsd.cnrs.fr.invalid (Raphaël Charron) 17 Mar 2025

    https://hal.science/hal-04993522v1
  • [hal-04321371] Origins and rate of mutations in bacteriophage Lambda

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Julien Lopez) 04 Dec 2023

    https://hal.science/hal-04321371v1
  • [hal-04688798] Comité français de cartographie

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Hélène Richard) 05 Sep 2024

    https://hal.science/hal-04688798v1
  • [hal-05036755] Bottom-up assembly of beneficial multi-species biofilms targeting undesirable bacteria using 3D fluorescence imaging

    Engineered synthetic microbial communities (SynComs) forming beneficial biofilms offer a promising strategy in biotechnology to prevent harmful bacterial settlement and reduce reliance on chemical antimicrobials. However, strain selection criteria and antagonistic mechanisms remain unclear. This study presents a bottom-up approach integrating 3D fluorescence imaging with high-throughput analysis of multi-strain biofilms. Our findings reveal that competitive strains against undesirable bacteria may also exclude beneficial ones, highlighting the need for compatibility control in SynCom assembly. SynComs composed of B. velezensis and Pediococcus spp. enhanced pathogen exclusion compared to single strains. Temporal analysis of biofilm interactions, supported by mathematical models, showed that pathogen exclusion was primarily driven by nutritional competition (Jameson effect) with additional specific interference mechanisms (prey-predator Lotka-Volterra model). Furthermore, pre-established SynComs significantly increased pathogen inhibition, indicating a distinct biofilm-associated exclusion effect. These insights provide a framework for SynCom assembly and refine our understanding of mechanisms driving beneficial biofilm applications.

    ano.nymous@ccsd.cnrs.fr.invalid (Virgile Guéneau) 16 Apr 2025

    https://hal.inrae.fr/hal-05036755v1
  • [hal-04283802] Polymerization of a bacterial actin-like MreB reveals actin-like and actin-unlike properties

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Wei Mao) 14 Nov 2023

    https://hal.inrae.fr/hal-04283802v1
  • [hal-04287124] Polymerization cycle of actin homolog MreB from a Gram-positive bacterium

    In most rod-shaped bacteria, the actin homologue MreB is an essential component of the protein complex effecting cell wall elongation. The polymerization cycle and filament properties of eukaryotic actin have studied for decades and are well characterized. However, purification and in vitro work on MreB proteins have proven very difficult. Current knowledge of MreB biochemical and polymerization properties remains limited and is based on MreB proteins from Gram-negative species. In this study, we report the first observation of organized filaments and the first 3D-structure of MreB from a Gram-positive bacterium. We have purified MreB from the thermophilic Geobacillus stearothermophilus and shown that it forms straight pairs of protofilaments in vitro, and that polymerization depends on the presence of both lipids and nucleotide triphosphate. Two spatially close short hydrophobic sequences mediate membrane anchoring. Importantly, we demonstrate that unlike eukaryotic actin, nucleotide hydrolysis is a prerequisite for MreB interaction with the membrane, and that binding to lipids then triggers polymerization. Based on our results, we propose a molecular model for the mechanism of MreB polymerization.

    ano.nymous@ccsd.cnrs.fr.invalid (Wei Mao) 15 Nov 2023

    https://hal.inrae.fr/hal-04287124v1
  • [hal-01204406] Fast solubilization of recalcitrant cellulosic biomass by the basidiomycete fungus [i]Laetisaria arvalis[/i] involves successive secretion of oxidative and hydrolytic enzymes

    Background: Enzymatic breakdown of lignocellulosic biomass is a known bottleneck for the production of high-value molecules and biofuels from renewable sources. Filamentous fungi are the predominant natural source of enzymes acting on lignocellulose. We describe the extraordinary cellulose-deconstructing capacity of the basidiomycete Laetisaria arvalis, a soil-inhabiting fungus. Results: The L. arvalis strain displayed the capacity to grow on wheat straw as the sole carbon source and to fully digest cellulose filter paper. The cellulolytic activity exhibited in the secretomes of L. arvalis was up to 7.5 times higher than that of a reference Trichoderma reesei industrial strain, resulting in a significant improvement of the glucose release from steam-exploded wheat straw. Global transcriptome and secretome analyses revealed that L. arvalis produces a unique repertoire of carbohydrate-active enzymes in the fungal taxa, including a complete set of enzymes acting on cellulose. Temporal analyses of secretomes indicated that the unusual degradation efficiency of L. arvalis relies on its early response to the carbon source, and on the finely tuned sequential secretion of several lytic polysaccharide monooxygenases and hydrolytic enzymes targeting cellulose. Conclusions: The present study illustrates the adaptation of a litter-rot fungus to the rapid breakdown of recalcitrant plant biomass. The cellulolytic capabilities of this basidiomycete fungus result from the rapid, selective and successive secretion of oxidative and hydrolytic enzymes. These enzymes expressed at critical times during biomass degradation may inspire the design of improved enzyme cocktails for the conversion of plant cell wall resources into fermentable sugars.

    ano.nymous@ccsd.cnrs.fr.invalid (David Navarro) 28 May 2020

    https://hal.science/hal-01204406v1
  • [hal-02868456] Conserved white rot enzymatic mechanism for wood decay in the Basidiomycota genus Pycnoporus

    White-rot (WR) fungi are pivotal decomposers of dead organic matter in forest ecosystems and typically use a large array of hydrolytic and oxidative enzymes to deconstruct lignocellulose. However, the extent of lignin and cellulose degradation may vary between species and wood type. Here we combined comparative genomics, transcriptomics and secretome proteomics to identify conserved enzymatic signatures at the onset of wood decaying activity within the Basidiomycota genus Pycnoporus. We observed strong conservation in the genome structures and the repertoires of protein coding genes across the four Pycnoporus species described to date, despite the species having distinct geographic distributions. We further analyzed the early response of P. cinnabarinus, P. coccineus and P. sanguineus to diverse (ligno)-cellulosic substrates. We identified a conserved set of enzymes mobilized by the three species for breaking down cellulose, hemicellulose and pectin. The co-occurrence in the exo-proteomes of H2O2 producing enzymes with H2O2 consuming enzymes was a common feature of the three species, although each enzymatic partner displayed independent transcriptional regulation. Finally, cellobiose dehydrogenase-coding genes were systematically co-regulated with at least one AA9 LPMO gene, indicative of enzymatic synergy in vivo. This study highlights a conserved core white-rot fungal enzymatic mechanism behind the wood decaying process.

    ano.nymous@ccsd.cnrs.fr.invalid (Shingo Miyauchi) 05 Jan 2024

    https://amu.hal.science/hal-02868456v2
  • [hal-01000933] Characterization of salt-adapted secreted lignocellulolytic enzymes from the mangrove fungus Pestalotiopsis sp

    Fungi are important for biomass degradation processes in mangrove forests. Given the presence of sea water in these ecosystems, mangrove fungi are adapted to high salinity. Here we isolate Pestalotiopsis sp. NCi6, a halotolerant and lignocellulolytic mangrove fungus of the order Xylariales. We study its lignocellulolytic enzymes and analyse the effects of salinity on its secretomes. De novo transcriptome sequencing and assembly indicate that this fungus possesses of over 400 putative lignocellulolytic enzymes, including a large fraction involved in lignin degradation. Proteomic analyses of the secretomes suggest that the presence of salt modifies lignocellulolytic enzyme composition, with an increase in the secretion of xylanases and cellulases and a decrease in the production of oxidases. As a result, cellulose and hemicellulose hydrolysis is enhanced but lignin breakdown is reduced. This study highlights the adaptation to salt of mangrove fungi and their potential for biotechnological applications.

    ano.nymous@ccsd.cnrs.fr.invalid (Yonathan Arfi) 07 Jan 2020

    https://hal.science/hal-01000933v1
  • [hal-04131544] Electrochemical biosensor based on NAD(P)H-dependent Quinone Reductase for rapid and efficient detection of vitamin K3

    Abstract Vitamin K refers to a group of vitamins that play an important role in blood coagulation and regulation of bone and vascular metabolism. However, vitamin K3 may give severe side effects in animal and humans when improperly added to food and feed due to its toxicity. Here, an electrochemical biosensor, based on the YaiB NADPH-dependent quinone reductase from Lactococcus lactis (YaiB), was developed to achieve rapid and redox probe-free detection of vitamin K3. First, we demonstrated the ability of the carbon electrode to distinguish between 1,4-benzoquinone and hydroquinone. Then, we engineered YaiB to work as a bioreceptor immobilized at the electrode and we demonstrated its sensitivity and specificity to reduce vitamin K3. Finally, to demonstrate the practical potential of the biosensor, we tested it directly in spiked milk samples, achieving 15-minute quantification of the vitamin K3. The limit of detection was 0.18μM and 0.86 μM in buffer and milk, respectively.

    ano.nymous@ccsd.cnrs.fr.invalid (Majd Khalife) 16 Jun 2023

    https://hal.inrae.fr/hal-04131544v1
  • [hal-04849575] Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in experimental COVID-19

    Aging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.

    ano.nymous@ccsd.cnrs.fr.invalid (Patrícia Brito Rodrigues) 19 Dec 2024

    https://hal.univ-lille.fr/hal-04849575v1
  • [hal-04986201] The mutational landscape of Bacillus subtilis conditional hypermutators shows how proofreading skews DNA polymerase error rates

    Polymerase errors during DNA replication are a major source of point mutations in genomes. The spontaneous mutation rate also depends on the counteracting activity of DNA repair mechanisms, with mutator phenotypes appearing constantly and allowing for periods of rapid evolution in nature and in the laboratory. Here, we use the Gram-positive model bacterium Bacillus subtilis to disentangle the contributions of DNA polymerase initial nucleotide selectivity, DNA polymerase proofreading, and mismatch repair (MMR) to the mutation rate. To achieve this, we constructed several conditional hypermutators with a proofreading-deficient allele of polC and/or a deficient allele of mutL and performed mutation accumulation experiments. These conditional hypermutators enrich the B. subtilis synthetic biology toolbox for directed evolution. Using mathematical models, we investigated how to interpret the apparent probabilities with which errors escape MMR and proofreading, highlighting the difficulties of working with counts that aggregate potentially heterogeneous mutations and with unknowns about the pathways leading to mutations in the wild-type. Aware of these difficulties, the analysis shows that proofreading prevents partial saturation of the MMR in B. subtilis and that an inherent drawback of proofreading is to skew the net polymerase error rates by amplifying intrinsic biases in nucleotide selectivity.

    ano.nymous@ccsd.cnrs.fr.invalid (Ira Tanneur) 11 Mar 2025

    https://hal.science/hal-04986201v1
  • [hal-04714371] Massive detection of cryptic recessive genetic defects in dairy cattle mining millions of life histories

    Background: Dairy cattle breeds are populations of limited effective size, subject to recurrent outbreaks of recessive defects that are commonly studied using positional cloning. However, this strategy, based on the observation of animals with characteristic features, may overlook a number of conditions, such as immune or metabolic genetic disorders, which may be confused with pathologies of environmental etiology. Results: We present a data mining framework specifically designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. Conclusions:The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

    ano.nymous@ccsd.cnrs.fr.invalid (Florian Besnard) 30 Sep 2024

    https://hal.inrae.fr/hal-04714371v1
  • [hal-04331718] Impact of plastics on the biogeochemical role of microorganisms in the marine environment

    [...]

    ano.nymous@ccsd.cnrs.fr.invalid (Pascal Conan) 08 Dec 2023

    https://hal.science/hal-04331718v1
  • [hal-03089431] BIOCHEMICAL CHARACTERISTICS OF A DIFFUSIBLE FACTOR THAT INDUCES GAMETOPHYTE TO SPOROPHYTE SWITCHING IN THE BROWN ALGA ECTOCARPUS

    The haploid-diploid life cycle of the filamentous brown alga Ectocarpus involves alternation between two independent and morphologically distinct multicellular generations, the sporophyte and the gametophyte. Deployment of the sporophyte developmental program requires two TALE homeodomain transcription factors OUROBOROS and SAMSARA. In addition, the sporophyte generation has been shown to secrete a diffusible factor that can induce uni-spores to switch from the gametophyte to the sporophyte developmental program. Here, we determine optimal conditions for production, storage and detection of this diffusible factor and show that it is a heat-resistant, high molecular weight molecule. Based on a combined approach involving proteomic analysis of sporophyte-conditioned medium and the use of biochemical tools to characterize arabinogalactan proteins, we present evidence that sporophyte-conditioned medium contains AGP epitopes and suggest that the diffusible factor may belong to this family of glycoproteins.

    ano.nymous@ccsd.cnrs.fr.invalid (Haiqin Yao) 28 Dec 2020

    https://cnrs.hal.science/hal-03089431v1
  • [hal-02936312] Aliments fermentés & bénéfices santé : un défi pour la recherche

    Depuis des millénaires, localement et à l’échelle internationale, existe dans notre diète une famille d’aliments particuliers : les aliments fermentés. Ces aliments « vivants », façonnés par des micro-organismes, ont des caractéristiques microbiologiques, biochimiques et physico-chimiques très différentes de la matière première dont ils sont issus. De ce fait, ils ont été parés de nombreuses vertus nutritionnelles et de santé bien que les études qui ont été réalisées sur ces aliments soient insuffisantes et peinent à esquisser un effet générique. Cependant, dans le contexte actuel des attentes de durabilité et de naturalité, il est clair que ces aliments pourraient avoir un rôle central à jouer dans nos systèmes alimentaires. La question de leur valeur santé, au regard notamment des nouvelles connaissances sur le microbiote intestinal, doit être clarifiée pour pouvoir considérer la place des aliments fermentés dans les recommandations alimentaires.

    ano.nymous@ccsd.cnrs.fr.invalid (Sylvie Lortal) 29 Nov 2021

    https://hal.science/hal-02936312v1

Contact

micalis@inra.fr