Role of listeriolysin O and phospholipases C in <i>L. monocytogenes</i> intercellular protrusion dynamics, resolution, and autophagy avoidance
Notice bibliographique
Résumé
ABSTRACT Cell-to-cell spread is a major mechanism used by the bacterial pathogen Listeria monocytogenes to disseminate within its host. In this mechanism, bacteria are directly transferred from the cytosol of an infected donor cell to a recipient cell via formation of an intercellular protrusion. The intercellular protrusion resolves into a vacuole that is disrupted by L. monocytogenes to reach the cytosol of the recipient cell, where it divides and starts new cell-to-cell spread cycles. Here, we studied the spatiotemporal dynamics of the donor and recipient host cell plasma membranes during intercellular protrusion formation, resolution, and disruption, as well as the role of the bacterial pore-forming toxin listeriolysin O (LLO) and two phospholipases C in these dynamics. Leveraging three-dimensional live-cell microscopy, we co-cultured and imaged infected epithelial cells expressing different fluorescent plasma membrane markers to distinguish donor from recipient cell membranes. We characterized, for the first time, the dynamics of the canonical cell-to-cell spread pathway in which protrusions resolve into double-membrane vacuoles, followed by the successive disruption of donor and recipient membranes. We found that LLO controls protrusion resolution into a double-membrane vacuole and disruption of donor and recipient membranes, whereas the phospholipases C (PLCs) control donor membrane disruption and prevent bacterial entrapment into autophagosomes. Furthermore, we identified a second, more efficient “non-canonical” cell-to-cell spread pathway strictly requiring LLO/PLCs cooperation, which resolves into a single-membrane vacuole that is rapidly disrupted. Altogether, this study provides the first detailed analysis of membrane dynamics within intercellular protrusions and vacuoles, establishing an advanced model for L. monocytogenes cell-to-cell spread. IMPORTANCE Intracellular bacterial pathogens, including L. monocytogenes , spread from cell to cell to effectively disseminate within host tissues and cause systemic infections. We developed a fluorescence microscopy-based method to visualize and distinguish in real time the dynamics of donor and recipient host cell plasma membranes during the different stages of the cell-to-cell spread process: (i) formation of the intercellular protrusion-containing L. monocytogenes , (ii) protrusion resolution into a vacuole, and (iii) disruption of the vacuolar membranes until the bacterium is released into the cytosol of the recipient cell. We measured the kinetics of the two identified—canonical and non-canonical—cell-to-cell spread pathways of L. monocytogenes in epithelial cells. This work also revealed that the virulence factors listeriolysin O and phospholipases C differentially control donor and recipient membrane remodeling and bacterial capture into autophagosomes, providing an advanced model for L. monocytogenes cell-to-cell spread.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 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 tête enseignante, 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 ».