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

The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD [document électronique] / Jim Sun, Auteur ; Alex Siroy, Auteur ; Ravi K. Lokareddy, Auteur . - Nature Publishing Group, 2015 . - p.672-678. - (Nature structural & molecular biology., ISSN 1545-9985; 22(9)) .
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