HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Uncovering a new family of conserved virulence factors that promote the production of host‐damaging outer membrane vesicles in gram‐negative bacteria
No full textInternational audienceCprA is a short‐chain dehydrogenase/reductase (SDR) that contributes to resistance against colistin and antimicrobial peptides. The cprA gene is conserved across Pseudomonas aeruginosa clades and its expression is directly regulated by the two‐component system PmrAB. We have shown that cprA expression leads to the production of outer membrane vesicles (OMVs) that block autophagic flux and have a greater capacity to activate the non‐canonical inflammasome pathway. In a murine model of sepsis, a P. aeruginosa strain deleted for cprA was less virulent than the wild‐type (WT) strain. These results demonstrate the important role of CprA in the pathogenicity of P. aeruginosa . It is worth noting that CprA is also a functional ortholog of hemolysin F (HlyF), which is encoded by virulence plasmids of Escherichia coli . We have shown that other cryptic SDRs encoded by mammalian and plant pathogens, such as Yersinia pestis and Ralstonia solanacearum are functional orthologs of CprA and HlyF. These SDRs also induce the production of OMVs which block autophagic flux. This study uncovers a new family of virulence determinants in Gram‐negative bacteria, offering potential for innovative therapeutic interventions and deeper insights into bacterial pathogenesis
Approach to anaemia in gastrointestinal disease: A position paper by the ESPGHAN Gastroenterology Committee
No full textInternational audienceAnaemia is a frequent consequence of many gastrointestinal (GI) diseases in children and it can even be the initial presenting symptom of underlying chronic GI disease. The definition of anaemia is age and gender-dependent and it can be classified based on pathophysiology, red cell morphology, and clinical presentation. Although nutritional deficiencies, including GI malabsorption of nutrients and GI bleeding, play a major role, other pathophysiologic mechanisms seen in chronic GI diseases, whether inflammatory (e.g., inflammatory bowel disease) or not (e.g., coeliac disease and dysmotility), are causing anaemia. Drugs, such as proton pump inhibitors, mesalamine, methotrexate and sulfasalazine, are also a potential cause of anaemia. Not uncommonly, due to a combination of factors, such as iron deficiency and a chronic inflammatory state, the underlying pathophysiology may be difficult to decipher and a broad diagnostic work-up is required. The goal of treatment is correction of anaemia by supplementation of iron and vitamins. The first therapeutic step is</div
Bacterial Conjugation in the Ruminant Pathogen Mycoplasma agalactiae is Influenced by Eukaryotic Host Factors
No full textInternational audienceABSTRACT Bacterial conjugation plays a pivotal role in the evolution and adaptation of genome-reduced mycoplasmas. Despite their fast evolution rate, the conjugative properties of these organisms remain largely understudied, particularly in vivo . In the present study, the ruminant pathogen Mycoplasma agalactiae was used as a model organism to document the conjugative properties of mycoplasmas in environments of increasing complexity, from axenic to cell and organotypic culture conditions. Compared to axenic mating conditions, mycoplasma co-cultivation with goat epithelial cells or bovine precision-cut lung slices (PCLS) resulted in enhanced mating frequencies with high rates of M. agalactiae Integrative and Conjugative Element (ICEA) self-dissemination. These results were conditioned by the presence of eukaryotic cells in the culture and influenced by competition between mating partners but were not limited to M. agalactiae , as similar results were observed with Mycoplasma bovis. Mycoplasma conjugation ex vivo was further characterized by analyzing mycoplasma chromosomal transfer (MCT), a newly discovered mechanism of horizontal exchange of chromosomal DNA that generates mosaic genomes. Although closely associated with ICEA transfer, MCT was detected at low rates under cell and organotypic culture conditions suggesting a complex interplay between these two conjugative processes or a poor viability of the MCT progeny. Finally, mating experiments under nutrient-deprived conditions identified nucleotide stress as a potential factor influencing the modulation of mycoplasma conjugation by eukaryotic host cells. In conclusion, these results suggest that horizontal gene transfer in vivo is likely underestimated and provide valuable models to further studying mycoplasma conjugation ex vivo . IMPORTANCE Conjugation is an evolutionary shortcut that bacteria use to exchange genetic information with their neighbors. Despite the fast evolution rate of the genome-reduced mycoplasmas, their conjugative properties remain largely understudied, particularly in vivo . Here we used the ruminant pathogen Mycoplasma agalactiae to study how mycoplasmas conjugate in co-culture with hosts-derived cells and tissues. Interestingly, conjugation was stimulated when mycoplasmas were co-cultured with eukaryotic cells. This was documented by monitoring the self-propagation of a mobile genetic element known as Integrative and Conjugative Element (ICE) and the exchange of chromosomal DNA leading to the formation of mosaic genomes. While ICE transfer was observed at high frequency, only a few mosaic genomes were detected in the presence of eukaryotic cells. Further data point towards nucleotide stress as a possible factor modulating mycoplasma conjugation in cellular environments. These results suggest that mycoplasma-host interactions may stimulate conjugation in vivo
Data from: Transgenerational transmission of an environmental modification in quails
No full textDataset : https://zenodo.org/records/15796146/files/pheno_data.tsv?download=1While epigenetic variations can contribute to shaping phenotypic diversity, it can be challenging to isolate and quantify the portion of trait variability under epigenetic influence. We compared the phenotypic response of two epilines of Japanese quails (Coturnix japonica), with similar genetic structure across three generations following an initial genistein ingestion in the ancestors’ diet. Measured phenotypes included body weight at various ages, egg production traits, tissue weight and behavioural traits
Sex-specific effects of a methionine-restricted maternal diet on liver transcript levels and fatty liver production in mule ducks
No full textInternational audienceSex-specific effects of maternal diet on offspring phenotypes have been reported in farm animals including in poultry. The present study was conducted in mule ducks, investigating the long-term effects of a methionine-restricted maternal diet on the production performance of the offspring of both sexes. Sixty female ducks were divided into two groups and fed either a control diet containing 4.0 g/kg of methionine or a restricted diet containing 2.5 g/kg of methionine. Next, 254 offspring were divided into four subgroups of 60-67 animals, according to maternal diet and sex. Their growth performance was recorded until 87 days of age. Then, plasma parameters were measured on these non-overfed ducks (NOFDs) at D87 and 60 of them were sacrificed, representing 15 males and 15 females in each maternal diet group. Carcass traits were recorded, and the liver transcript level of 170 genes mainly involved in energy or one-carbon metabolism was studied. The remaining 194 ducks were overfed during 12.5 days-until 100 days of age-for fatty liver production. Then, zootechnical traits and plasma parameters were measured on these 194 overfed ducks (OFDs), and the liver transcript level of the same 170 genes was studied. The results showed that the methionine-restricted maternal diet affected traits in NOFDs but in females only, with lower liver lipid and DM percentages (P-value = 0.006 and P-value = 0.004, respectively) and a lower plasma cholesterol level (P-value = 0.020). In OFDs, after the overfeeding period, fatty liver weight was reduced in both sexes by around 53 g, or almost 10% (P-value = 0.016 and 0.017 in females and males, respectively). Only females showed a tendency to lower liver lipid and DM percentages (P-value = 0.078 and P-value = 0.062, respectively) and their plasmatic aspartate aminotransferase activity was reduced (P-value = 0.025). In addition, 18 genes differentially expressed between maternal diet groups were identified in the liver of females only. All were up-regulated in the restricted group and involved in either energy or one-carbon metabolism. These findings showed that the methioninerestricted maternal diet had long-term effects on liver traits, impacting production performance in both sexes. Importantly, these effects were sex-specific, and robust enough to still be observed after the overfeeding period, despite the major reorganisation of metabolic pathways this implied
Étude du rôle des zoos dans la conservation de la faune sauvage française : mise en pratique avec l’élevage conservatoire du zoo african safari
No full textFaced with the erosion of biodiversity, zoos have a key role to play in the conservation of endangered species. In France, many zoos provide facilities for local wildlife. Among 24 projects targeting a species of French wildlife, 21 include in-situ conservation actions, and 9 captive breeding. African Safari, a zoo located near Toulouse, wishes to take part in the conservation of a native species, through the establishment of a captive breeding program. A selection was made based on the species' inclusion in a National Action Plan (PNA), their size, geographic distribution, and planned actions under the PNA, leading to the choice of the Pyrenean Desman. Drawing on bibliographic data and feedback from previous experiences (including compiled information on the Desman’s ecology as well as past attempts at captive breeding and reproduction), a captive breeding proposal was formulated by African Safari. The project's conservation implications and the resources required were also assessed.Face à l’érosion de la biodiversité, les zoos ont un rôle clé à jouer dans la conservation des espèces menacées. En France, beaucoup de zoos mettent à disposition des installations pour la faune sauvage locale. Parmi 24 projets répertoriés et ciblant une espèce de la faune française, 21 incluent des actions in-situ, et 9 un élevage conservatoire. L’African Safari, parc zoologique près de Toulouse, souhaite s’engager dans la sauvegarde d’une espèce autochtone notamment via un élevage conservatoire. Une sélection a été faite selon l’appartenance à un PNA, le gabarit, la répartition géographique et les actions prévues par le PNA, conduisant à retenir le Desman des Pyrénées. À partir de données bibliographiques et de retours d’expérience (écologie du Desman et tentatives d’élevage et de reproduction en captivité), une proposition d’élevage conservatoire a été formulée par le parc. Les implications du projet en termes de conservation et de ressources nécessaires ont aussi été évaluées
Unveiling how mitotic spindle orientation in 3D human colon organoids affects matrix displacements through a 4D study using DVC
No full textInternational audienceCell division is a major event in tissue homeostasis, enabling renewal and regeneration. In human colon, vertical division is mainly observed in the stem cell compartment while horizontal division is more frequent in the progenitor transit amplifying zone. To study cell division, the human colon epithelium represents a relevant model due to its rapid renewal and high number of mitoses. Studying live mechanical interactions between the epithelium and its matrix in vivo is challenging due to the lack of suitable methods. Colon organoids seeded in Matrigel are good models because they recapitulate the organization and properties of tissue architecture. This culture set-up allows to study the displacements of the matrix around the organoid. We studied the impact of cell division within the human colonic epithelium on the extracellular matrix. We validated an original experimental and analytical process with 3D time-lapse confocal microscopy to follow cell division and matrix displacements, on which we performed a 4D Digital Volume Correlation. Depending on the orientation of the mitotic spindle, cell division affects the matrix differently. Vertical division causes a predominantly uniaxial displacement of the matrix, while horizontal division involves a multiaxial and wider displacement
Le séquençage à longue lecture de l'opéron 16S-ITS-23S permet d'étudier la transmission du microbiote maternel avec une résolution au niveau de la pseudo-souche
No full textInternational audienceWe developed an optimized bioinformatics pipeline to analyze PacBio HiFi long reads targeting the 16S-ITS-23S region, enabling fine taxonomic resolution down to the level of putative strains. This processing workflow includes quality control (FastQC, MultiQC), denoising with Swarm using various clustering parameters, chimera detection and removal with VSEARCH, and filtering of ASVs based on minimum abundance and presence across multiple samples to ensure biological robustness. Taxonomic affiliation is performed against the GTDB database, with low-confidence identifications (<90% identity) relabeled as “weak affiliation.” To group ASVs into putative strains, we apply hierarchical clustering based on Pearson correlation of abundance profiles (threshold 0.9). This approach allowed, for example, the clustering of 108 ASVs assigned to Escherichia coli into 45 distinct strains. Despite the high computational cost of the process (up to 41 CPU days for fine-resolution clustering), this pipeline provides a putative strain × abundance matrix suitable for studying maternal microbial transmission to piglets. Results show that transmission occurs predominantly during lactation, with about 2.7% of the initial maternal strains persisting until weaning, and a higher proportion of strains shared between piglets and their own mother compared to unrelated sows.Nous avons développé une pipeline bioinformatique optimisée pour analyser les lectures longues PacBio HiFi ciblant la région 16S-ITS-23S, permettant une résolution taxonomique fine jusqu’au niveau des pseudo-souches. Cette chaîne de traitement inclut un contrôle qualité (FastQC, MultiQC), un débruitage via Swarm avec différents paramètres de clustering, une détection et suppression des chimères par VSEARCH, ainsi qu’un filtrage des ASVs selon leur abondance minimale et leur présence dans plusieurs échantillons pour garantir la robustesse biologique. L’affiliation taxonomique est réalisée contre la base GTDB, avec un renommage des identifications faibles (<90 % d’identité) en « weak affiliation ». Pour regrouper les ASVs en pseudo-souches, nous utilisons un clustering hiérarchique basé sur la corrélation de Pearson des profils d’abondance (seuil 0,9). Cette approche a permis, par exemple, de regrouper 108 ASVs assignés à Escherichia coli en 45 souches distinctes. Malgré la forte charge computationnelle du traitement (jusqu’à 41 jours CPU pour le clustering à la résolution fine), ce pipeline fournit une matrice pseudo-souche × abondance exploitable pour étudier la transmission microbienne maternelle aux porcelets. Les résultats montrent que la transmission s’effectue majoritairement durant la lactation, avec environ 2,7 % des souches maternelles initiales persistant jusqu’au sevrage, et une plus grande part des souches partagées entre porcelets et leur mère comparé à des truies non apparentées
Bispecific nanobody® as a new pharmacological drug for the selective inhibition of Trypsin‐3
No full textInternational audienceBackground and Purpose Proteolytic balance is dysregulated in many diseases, with proteases playing critical roles in pathological pathways. A high level of Trypsin‐3 expression has been implicated as a significant mediator of tumour progression and metastasis, and this protease is associated with poor prognosis for patients in various cancers. Therefore, Trypsin‐3 inhibition has emerged as a promising therapeutic target. However, no physiological or pharmacological inhibitor has yet been described that specifically targets Trypsin‐3. A major challenge in developing a druggable inhibitor for this protease lies in achieving selectivity, as proteases belong to a large enzymatic family with close homologues that share similarities in the three‐dimensional folding of their active conformation. Experimental Approach An advanced screening strategy of a large library of synthetic humanised nanobodies was employed to isolate highly selective recombinant antibodies targeting the active conformation of Trypsin‐3. Among five hits, we combined two domains with distinct paratopes and inhibitory mechanisms to generate a macrodrug candidate capable to efficiently block Trypsin‐3 activity. Key Results This bispecific nanobody demonstrated exceptionally high selectivity and affinity for Trypsin‐3 in vitro, as well as a strong ability to inhibit cancer cell migration ex vivo for the PC‐3 cancer cell line. Conclusions and Implications This study underscores the versatility and potential of synthetic nanobody engineering in the development of highly selective protease inhibitors, paving the way for their consideration as drug candidates for clinical development
Les poules: Comprendre leur diversité génétique visible
No full textNational audienceFollowing chicken domestication, breeds were differentiated by visible characteristics such as plumage color or crest shape, as a result of breeders' choices. The genetic determinism of these traits was studied in the early 20th century by genetic pioneers, who proposed the existence of major genes. In 2004, sequencing of the chicken genome made it possible to precisely identify the genes responsible for visible traits. This book revisits the visible genetic diversity of hens, explaining the mechanisms leading to the variations observed. It also looks at the genetic determinism of certain metabolic defects. It presents the fundamental principles of Mendelian genetics, uses pedagogical diagrams to explain the interactions between genes or between genes and the environment, and describes over 30 genes that breeders acted on before they were able to identify them. Molecular diagnostic tests can be proposed to help interpret phenotypes, for example in the case of crossbreeding.Abundantly illustrated, this book is aimed at amateur or industrial breeders, teachers at general or agricultural high schools, and researchers interested in comparative genetics between birds and mammals.Après la domestication de la poule, des races ont été différenciées par des caractères visibles tels que la couleur du plumage ou la forme de la crête, sous l’effet des choix des éleveurs. Le déterminisme génétique de ces caractères a été étudié, au début du XXe siècle, par des pionniers de la génétique, qui ont proposé l’existence de gènes à effets majeurs. En 2004, le séquençage du génome de la poule a révolutionné l’étude de la domestication et de la diversité génétique des races, permettant de reconstituer leur histoire et d’identifier précisément les gènes responsables des caractères visibles. Des tests de diagnostic moléculaire peuvent proposés pour faciliter l’interprétation des phénotypes, par exemple dans le cas de croisements. Reprenant la structure du livre de Gérard Coquerelle paru aux éditions de l’Inra en 2000, en y intégrant les connaissances apportées par la génétique moléculaire, cet ouvrage revisite la diversité génétique visible des poules en expliquant les mécanismes conduisant aux variations observées. Il aborde aussi le déterminisme génétique de certains défauts métaboliques. Il présente les principes fondamentaux de la génétique mendélienne, éclaire/vulgarise par des schémas pédagogiques les interactions entre gènes ou entre gènes et milieu, et décrit plus de 30 gènes, sur lesquels les éleveurs ont agi avant de pouvoir les connaître. Abondamment illustré, ce livre s’adresse aux éleveurs amateurs ou industriels, aux enseignants en lycée général ou lycée agricole et aux chercheurs intéressés par la génétique comparée entre oiseaux et mammifères