Titre :

Targeting Type IV pili as an antivirulence strategy against invasive meningococcal disease

Auteur(s) :

Denis, Kevin [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Le Bris, Marion [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Le Guennec, Loïc [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Barnier, Jean-Philippe [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Faure, Camille [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Gouge, Anne [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Bouzinba-Ségard, Haniaa [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Jamet, Anne [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Euphrasie, Daniel [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Durel, Beatrice [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Barois, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Pelissier, Philippe [Auteur]
Centre hospitalier Saint-Joseph [Paris]
Morand, Philippe C. [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Coureuil, Mathieu [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Lafont, Frank [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Join-Lambert, Olivier [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Nassif, Xavier [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Bourdoulous, Sandrine [Auteur correspondant]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]

Titre de la revue :

Nature Microbiology

Pagination :

972-984

Éditeur :

Nature Publishing Group

Date de publication :

2019-06

ISSN :

2058-5276

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Mycologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Protistologie

Résumé en anglais : [en]

Bacterial virulence factors are attractive targets for the development of therapeutics. Type IV pili, which are associated with a remarkable array of properties including motility, the interaction between bacteria and ...
Lire la suite >Bacterial virulence factors are attractive targets for the development of therapeutics. Type IV pili, which are associated with a remarkable array of properties including motility, the interaction between bacteria and attachment to biotic and abiotic surfaces, represent particularly appealing virulence factor targets. Type IV pili are present in numerous bacterial species and are critical for their pathogenesis. In this study, we report that trifluoperazine and related phenothiazines block functions associated with Type IV pili in different bacterial pathogens, by affecting piliation within minutes. Using Neisseria meningitidis as a paradigm of Gram-negative bacterial pathogens that require Type IV pili for pathogenesis, we show that piliation is sensitive to altered activity of the Na+ pumping NADH–ubiquinone oxidoreductase (Na+−NQR) complex and that these compounds probably altered the establishment of the sodium gradient. In vivo, these compounds exert a strong protective effect. They reduce meningococcal colonization of the human vessels and prevent subsequent vascular dysfunctions, intravascular coagulation and overwhelming inflammation, the hallmarks of invasive meningococcal infections. Finally, they reduce lethality. This work provides a proof of concept that compounds with activity against bacterial Type IV pili could beneficially participate in the treatment of infections caused by Type IV pilus-expressing bacteriaLire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Projet ANR :

SATT ERGANEO (EX IDF INNOV)
Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL