A40 GUT MICROBIOTA PROMOTES NUTRIENT AVAILABLITY AND PATHOGENESIS OF AN ATTACHING/ EFFACING BACTERIAL PATHOGEN
Notice bibliographique
Résumé
Abstract Background Our gut microbiota plays an important role in protecting the gastrointestinal (GI) tract from invading enteric pathogens. Much of this colonization resistance is mediated by limiting nutrient availability, however, enteric pathogens have evolved strategies to subvert this competition, utilizing commensal metabolites to facilitate their infection. Access to nutrients is not only crucial for a pathogen’s metabolic fitness, but can also drive the expression of virulence factors, a process high in energy demands. In addition, enteric pathogens, such as the attaching and effacing (A/E) bacterium Citrobacter rodentium, must cross the colonic mucus layer that normally prevents their direct access to the underlying epithelium. Intestinal mucus is comprised of highly glycosylated mucins, with the sugar sialic acid frequently occupying the terminal position of their O-glycan side chains. We hypothesize that C. rodentium utilizes commensal-liberated mucin sugars, such as sialic acid, as nutrients and signals to promote its virulence. Purpose This study investigates the mechanisms by which A/E pathogens reach the colonic mucosal surface, and the role played by commensal microbes in facilitating the infection. Method Expression of virulence factors secreted by C. rodentium in the presence or absence of sialic acid was analyzed by SDS-PAGE and mass spectrometry. Next, we infected specific-pathogen free (SPF), germfree (GF), and previously GF C57Bl/6 mice mono-colonized with Bacteroides thetaotaomicron, a mucus-degrading commensal, to examine their susceptibility to C. rodentium and to measure the levels of free sialic acid in their feces. Result(s) Sensing of sialic acid by C. rodentium, was found to induce the secretion of several key virulence proteins, enhancing the pathogen’s migration across the colonic mucus layer and adhesion to the underlying epithelium. Access to sialic acid within the gut environment was enhanced in the presence of microbiota, as the levels of free sialic acid were low in GF mice. Interestingly, despite GF mice carrying very high C. rodentium burdens, passage across the mucus layer and infection of their colonic epithelium was impaired as compared to SPF mice. Notably, B. thetaotaomicron was found to degrade whole mucus in vitro, facilitating its consumption by C. rodentium for growth, while B. thetaotaomicron mono-colonized GF mice showed increased susceptibility to colonic infection by C. rodentium. Conclusion(s) We demonstrate that although commensal microbes promote colonization resistance, as an A/E pathogen infection establishes, specific commensal bacteria accelerate infection in the GI tract by releasing an important nutrient, ie. sialic acid, from mucus. Access to sialic acid promotes C. rodentium virulence by inducing the key virulence factors that facilitate its translocation across the mucus layer as well as adhesion to the epithelium, thereby expediting disease progression. Please acknowledge all funding agencies by checking the applicable boxes below CCC, CIHR, Other Please indicate your source of funding; CH.I.L.D. Foundation Disclosure of Interest None Declared
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».