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Cell wall peptidolipids of Mycobacterium avium: from genetic prediction to exact structure of a nonribosomal peptide
Authors:John P. Bannantine  Gilles Etienne  Françoise Laval  Judith R. Stabel  Anne Lemassu  Mamadou Daffé  Darrell O. Bayles  Christelle Ganneau  Frédéric Bonhomme  Maxime Branger  Thierry Cochard  Sylvie Bay  Franck Biet
Affiliation:1. National Animal Disease Center, USDA‐Agricultural Research Service, Ames, IA, 50010, USA;2. Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France;3. Université de Toulouse, UPS, IPBS, Toulouse, 31000, France;4. Institut Pasteur, Unité Chimie des Biomolécules, France;5. CNRS UMR 3523, France;6. Infectiologie et Santé Publique, INRA, Université de Tours, UMR1282, Nouzilly, F‐37380, France
Abstract:Mycobacteria have a complex cell wall structure that includes many lipids; however, even within a single subspecies of Mycobacterium avium these lipids can differ. Total lipids from an M. avium subsp. paratuberculosis (Map) ovine strain (S‐type) contained no identifiable glycopeptidolipids or lipopentapeptide (L5P), yet both lipids are present in other M. avium subspecies. We determined the genetic and phenotypic basis for this difference using sequence analysis as well as biochemical and physico‐chemical approaches. This strategy showed that a nonribosomal peptide synthase, encoded by mps1, contains three amino acid specifying modules in ovine strains, compared to five modules in bovine strains (C‐type). Sequence analysis predicted these modules would produce the tripeptide Phe‐N‐Methyl‐Val‐Ala with a lipid moiety, termed lipotripeptide (L3P). Comprehensive physico‐chemical analysis of Map S397 extracts confirmed the structural formula of the native L3P as D‐Phe‐N‐Methyl‐L‐Val‐L‐Ala‐OMe attached in N‐ter to a 20‐carbon fatty acid chain. These data demonstrate that S‐type strains, which are more adapted in sheep, produce a unique lipid. There is a dose‐dependent effect observed for L3P on upregulation of CD25+ CD8 T cells from infected cows, while L5P effects were static. In contrast, L5P demonstrated a significantly stronger induction of CD25+ B cells from infected animals compared to L3P.
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