| Identification and structural characterization of an unusual mycobacterial monomeromycolyl-diacylglycerol. | |
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MedLine Citation:
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PMID: 16091048 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Systematic thin layer chromatographic (TLC) analysis of apolar lipids in Mycobacterium kansasii revealed the presence of a previously uncharacterized novel component. The product was ubiquitously found in a panel of M. kansasii clinical isolates, as well as other pathogenic and non-pathogenic mycobacterial species. TLC analysis of [(14)C]-acetate- or [(14)C]-glycerol-labelled M. kansasii cultures tentatively assigned the novel product as an unusual triacylglycerol-related lipid. Subsequent purification, followed by structural determination using (1)H-nuclear magnetic resonance (NMR) and electrospray mass spectrometry (ES/MS), led to the identification of this product as a monomeromycolyl-diacylglycerol (MMDAG). Treatment of M. kansasii with either isoniazid (INH), a well-known type II fatty acid synthase (FAS-II) and mycolic acid biosynthesis inhibitor, or tetrahydrolipstatin (THL), a drug approved for treating obesity, correlated with a reduced incorporation of [(14)C]-acetate into both mycolic acids and MMDAG. Addition of INH or THL to the cultures induced major morphological changes and, surprisingly, resulted in an increased number of lipid storage bodies, as determined by electron microscopy. The potent antimycobacterial activity of THL was confirmed against a variety of mycobacterial species, including INH-susceptible and -resistant Mycobacterium tuberculosis strains. Therefore, THL and other beta-lactones may be promising drugs for the development of new antitubercular therapy. |
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Authors:
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Laurent Kremer; Chantal de Chastellier; Gary Dobson; Kevin J C Gibson; Pablo Bifani; Stéphanie Balor; Jean-Pierre Gorvel; Camille Locht; David E Minnikin; Gurdyal S Besra |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular microbiology Volume: 57 ISSN: 0950-382X ISO Abbreviation: Mol. Microbiol. Publication Date: 2005 Aug |
Date Detail:
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Created Date: 2005-08-10 Completed Date: 2005-12-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8712028 Medline TA: Mol Microbiol Country: England |
Other Details:
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Languages: eng Pagination: 1113-26 Citation Subset: IM |
Affiliation:
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Laboratoire des Mécanismes Moléculaires de la Pathogénie Microbienne, INSERM U629, Institut Pasteur de Lille, 1, rue du Prof. Calmette, F-59019 Lille, France. laurent.kremer@univ-montp2.fr |
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Obesity Agents
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pharmacology Antitubercular Agents / chemistry, pharmacology* Diglycerides / biosynthesis*, chemistry* Drug Design Enzyme Inhibitors / pharmacology Fatty Acid Synthetase Complex / antagonists & inhibitors Isoniazid / pharmacology Lactones / pharmacology Lipids / biosynthesis Magnetic Resonance Spectroscopy Molecular Structure Mycobacterium kansasii / drug effects, metabolism*, ultrastructure Spectrometry, Mass, Electrospray Ionization Triglycerides / biosynthesis*, chemistry*, isolation & purification |
| Chemical | |
Reg. No./Substance:
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0/Anti-Obesity Agents; 0/Antitubercular Agents; 0/Diglycerides; 0/Enzyme Inhibitors; 0/Lactones; 0/Lipids; 0/Triglycerides; 54-85-3/Isoniazid; 96829-58-2/orlistat; EC 6.-/Fatty Acid Synthetase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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