<i>Giardia</i> extracellular vesicles disrupt intestinal epithelial junctions and inhibit the growth of commensal bacteria while increasing their swimming motility
Notice bibliographique
Résumé
Introduction Extracellular vesicles (EVs) have emerged as important mediators of host‐parasite interactions. The protozoan parasite Giardia duodenalis , the most common cause of parasitic diarrheal diseases worldwide, produces EVs in response to changes in the environment. The exact role of EVs in the pathogenesis of giardiasis remains unclear. In this study, we investigate the effects of EVs on the intestinal barrier such as the intestinal epithelium and the gut commensal bacteria. Disruption of the intestinal barrier has been implicated in the development of post‐giardiasis gut disorders and EVs may represent a novel mechanism of this disruption. Aims The aim of this research is to characterize Giardia EVs and investigate their effect on the host epithelium and commensal gut bacteria. Methods G. duodenalis (isolate NF) trophozoites were either incubated with 10X bile for 1 hour or left untreated and EVs were isolated using Qiagen Exo‐Easy Maxi Kit. The concentration and size of EVs were assessed using Nanosight track analysis (NTA). Proteomic analysis of EVs was conducted using liquid chromatography with tandem mass spectrometry. The effects of Giardia EVs on the host epithelium were assessed by exposing epithelial primary cell line (SCBN) to EVs for 24 hours and examining the tight junction proteins ZO‐1 and claudin‐4 by fluorescence microscopy. Antibacterial effect of Giardia EVs was assessed on gut commensals such as Escherichia coli strain HB101 and strain K12, Enterobacter cloacae (human isolate) and Enterococcus faecalis (human isolate) by measuring bacterial kinetic growth for 12 hours. Swimming motility of non‐invasive commensals was assessed on 0.3% agar after incubating with EVs for 24 hours and the halo sizes were measured as a marker of swimming behavior. Results Our findings indicate that bile treated Giardia trophozoites produce more EVs as compared to untreated trophozoites. NTA revealed that Giardia EVs range around 200 nm. Proteomic analysis of EVs revealed the presence of well characterized Giardia virulence factors such as cysteine proteases, tenascins, oxidative defense enzymes, variant surface proteins as well as metabolic enzymes such as arginine deaminase and ornithine carbamoyl transferase. Additionally, exposure of SCBN cells to EVs resulted in the disruption and/or rearrangement of tight junction proteins Zo‐1 and Claudin‐4. Moreover, our results also indicate that Giardia EVs exert bacteriostatic effects on E. coli strains HB101, K12, E. cloacae and E. faecalis. Finally, Giardia EVs also significantly increased the swimming motility of non‐invasive commensals E. coli strain HB101 and E. cloacae . Conclusion Our research highlights a novel mechanism of Giardia’s interaction with the intestinal barrier. Giardia EVs contain virulence factors that disrupt the host’s intestinal epithelium and modify the growth and motility of commensal bacteria. These effects may have significant implications in disease pathophysiology. Support or Funding Information Natural Sciences and Engineering Research Council (NSERC)
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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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,001 |
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 ».