| Titre : |
The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD |
| Type de document : |
document électronique |
| Auteurs : |
Jim Sun, Auteur ; Alex Siroy, Auteur ; Ravi K. Lokareddy, Auteur |
| Editeur : |
Nature Publishing Group |
| Année de publication : |
2015 |
| Collection : |
Nature structural & molecular biology., ISSN 1545-9985 num. 22(9) |
| Importance : |
p.672-678 |
| Langues : |
Anglais moyen (ca.1100-1500) (enm) |
| Catégories : |
[DIVERS] discipline médicale, paramédicale et scientifique:biochimie
[TUBER] cause:bacille de Koch
|
| Index. décimale : |
TU 5.3. Biologie moléculaire (résistance) / microbiologie |
| Résumé : |
Mycobacterium tuberculosis (Mtb) induces necrosis of infected cells to evade immune responses. Recently, we found that Mtb utilizes the protein CpnT to kill human macrophages by secreting its C-terminal domain, named tuberculosis necrotizing toxin (TNT) that induces necrosis by an unknown mechanism. Here we show that TNT gains access to the cytosol of Mtb-infected macrophages, where it hydrolyzes the essential co-enzyme nicotinamide adenine dinucleotide (NAD+). Expression or injection of a non-catalytic TNT mutant showed no cytotoxicity in macrophages or zebrafish zygotes, respectively, demonstrating that the NAD+-glycohydrolase activity is required for TNT-induced cell death. To prevent self-poisoning, Mtb produces an immunity factor for TNT (IFT) that binds TNT and inhibits its activity. The crystal structure of the TNT-IFT complex revealed a novel NAD+-glycohydrolase fold of TNT, which constitutes the founding member of a toxin family wide-spread in pathogenic microorganisms. |
| En ligne : |
https://doi.org/10.1038/nsmb.3064 |
| Format de la ressource électronique : |
HTML, PDF |
| Permalink : |
https://biblio.fares.be/opac_css/index.php?lvl=notice_display&id=9406 |
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