The Mycobacterium tuberculosis transcriptional ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
The Mycobacterium tuberculosis transcriptional repressor EthR is negatively regulated by Serine/Threonine phosphorylation
Auteur(s) :
Leiba, Jade [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Carrere-Kremer, Severine [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Blondiaux, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dimala, Martin Moune [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wohlkönig, Alexandre [Auteur]
Structural Biology Brussels [SBB]
Baulard, Alain [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Kremer, Laurent [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Molle, Virginie [Auteur correspondant]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Carrere-Kremer, Severine [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Blondiaux, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dimala, Martin Moune [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wohlkönig, Alexandre [Auteur]
Structural Biology Brussels [SBB]
Baulard, Alain [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Kremer, Laurent [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Molle, Virginie [Auteur correspondant]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Titre de la revue :
Biochemical and Biophysical Research Communications
Pagination :
1132-1138
Éditeur :
Elsevier
Date de publication :
2014-04
ISSN :
0006-291X
Mot(s)-clé(s) en anglais :
EthR
Ethionamide
Mycobacterium
Phosphorylation
Ser/Thr protein kinases
Ethionamide
Mycobacterium
Phosphorylation
Ser/Thr protein kinases
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologie
Résumé en anglais : [en]
Recent efforts have underlined the role of Serine/Threonine Protein Kinases (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein, we demonstrated that the Mycobacterium tuberculosis EthR, a ...
Lire la suite >Recent efforts have underlined the role of Serine/Threonine Protein Kinases (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein, we demonstrated that the Mycobacterium tuberculosis EthR, a transcriptional repressor that regulates the activation process of the antitubercular drug ethionamide (ETH) is a specific substrate of the mycobacterial kinase PknF. ETH is a prodrug that must undergo bioactivation by the monooxygenease EthA to exert its antimycobacterial activity and previous studies reported that EthR represses transcription of ethA by binding to the ethA-ethR intergenic region. Mass spectrometry analyses and site-directed mutagenesis identified a set of four phosphoacceptors, namely Thr2, Thr3, Ser4 and Ser7. This was further supported by the complete loss of PknF-dependent phosphorylation of a phosphoablative EthR mutant protein. Importantly, a phosphomimetic version of EthR, in which all phosphosites were replaced by Asp residues, exhibited markedly decreased DNA-binding activity compared with the wild-type protein. Together, these findings are the first demonstration of EthR phosphorylation and indicate that phosphorylation negatively affects its DNA-binding activity, which may impact ETH resistance levels in M. tb.Lire moins >
Lire la suite >Recent efforts have underlined the role of Serine/Threonine Protein Kinases (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein, we demonstrated that the Mycobacterium tuberculosis EthR, a transcriptional repressor that regulates the activation process of the antitubercular drug ethionamide (ETH) is a specific substrate of the mycobacterial kinase PknF. ETH is a prodrug that must undergo bioactivation by the monooxygenease EthA to exert its antimycobacterial activity and previous studies reported that EthR represses transcription of ethA by binding to the ethA-ethR intergenic region. Mass spectrometry analyses and site-directed mutagenesis identified a set of four phosphoacceptors, namely Thr2, Thr3, Ser4 and Ser7. This was further supported by the complete loss of PknF-dependent phosphorylation of a phosphoablative EthR mutant protein. Importantly, a phosphomimetic version of EthR, in which all phosphosites were replaced by Asp residues, exhibited markedly decreased DNA-binding activity compared with the wild-type protein. Together, these findings are the first demonstration of EthR phosphorylation and indicate that phosphorylation negatively affects its DNA-binding activity, which may impact ETH resistance levels in M. tb.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Source :