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Negative regulation by Ser/Thr phosphorylation of HadAB and HadBC dehydratases from Mycobacterium tuberculosis type II fatty acid synthase system.
MedLine Citation:
PMID:  21819969     Owner:  NLM     Status:  Publisher    
The type II fatty acid synthase system of mycobacteria is involved in the biosynthesis of major and essential lipids, mycolic acids, key-factors of Mycobacterium tuberculosis pathogenicity. The remarkable survival ability of M. tuberculosis in infected hosts is related to the presence of cell wall-associated mycolic acids. Despite their importance, the mechanisms that modulate expression of these lipids in response to environmental changes are unknown. We demonstrate here that HadAB and HadBC dehydratases of this system are phosphorylated by Ser/Thr protein kinases, which negatively affects their enzymatic activity. The phosphorylation of HadAB/BC is growth phase-dependent, suggesting that it represents a mechanism by which mycobacteria might tightly control mycolic acid biosynthesis under non-replicating condition. This study also suggests that phosphorylation of HadAB/BC may represent an unusual mechanism that allows M. tuberculosis to regulate its mycolic acid content, thus offering a new approach to future anti-tuberculosis drug development.
Nawel Slama; Jade Leiba; Nathalie Eynard; Mamadou Daffé; Laurent Kremer; Annaïk Quémard; Virginie Molle
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-27
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-8-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Département Mécanismes Moléculaires des Infections Mycobactériennes, 205 route de Narbonne, F-31077 Toulouse, France; Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
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