| The fatty acyl chains of Mycobacterium marinum lipooligosaccharides:structure, localization and acylation by PapA4 (MMAR_2343). | |
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MedLine Citation:
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PMID: 21803773 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We have recently established the fine structure of the glycan backbone of lipooligosaccharides (LOS-I to LOS-IV) isolated from Mycobacterium marinum, a close relative of Mycobacterium tuberculosis. These studies culminated with the description of an unusual terminal N-acylated monosaccharide that confers important biological functions to LOS-IV, such as macrophage activation that may be relevant to granuloma formation. It was, however, also suggested that the lipid moiety was required for LOSs to exert their immunomodulatory activity. Herein, using highly purified LOSs from M. marinum, we have determined through a combination of mass spectrometric and NMR techniques, the structure and localization of the fatty acids composing the lipid moiety. The occurrence of two distinct polymethyl-branched fatty acids presenting specific localizations is consistent with the presence of two highly related polyketide synthases (Pks5 and Pks5.1) in M. marinum, and presumably involved in the synthesis of these fatty acyl chains. In addition, a bioinformatic search permitted us to identify a set of enzymes potentially involved in the biosynthesis or transfer of these lipids to the LOS trehalose unit. These include MMAR_2343, a member of the polyketide-associated protein (Pap) family, that acylates trehalose-based glycolipids in M. marinum. The participation of MMAR_2343 to LOS assembly was demonstrated using a M. marinum mutant carrying a transposon insertion in the MMAR_2343 gene. Disruption of MMAR_2343 resulted in a severe LOS breakdown, indicating that MMAR_2343, designated hereafter PapA4, fulfills the requirements for LOS acylation and assembly. |
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Authors:
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Yoann Rombouts; Laeticia Alibaud; Séverine Carrère-Kremer; Emmanuel Maes; Caroline Tokarski; Elisabeth Elass; Laurent Kremer; Yann Guérardel |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-29 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-8-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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UGSF, CNRS UMR 8576, France; |
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