Cell wall peptidolipids of Mycobacterium avium: from genetic prediction to exact structure of a nonribosomal peptide

• DOI: 10.1111/mmi.13717
• Publication Date: 2017-05-30T16:22:56Z
• 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
• Keywords: Nonribosomal peptide; Mycobacterium avium complex

Mycobacteria have a complex cell wall structure that includes many lipids; however, even within single subspecies of Mycobacterium avium these lipids can differ. Total from an M. subsp. paratuberculosis (Map) ovine strain (S-type) contained no identifiable glycopeptidolipids or lipopentapeptide (L5P), yet both are present in other subspecies. We determined the genetic and phenotypic basis for this difference using sequence analysis as well biochemical physico-chemical approaches. This strategy showed nonribosomal peptide synthase, encoded by mps1, contains three amino acid specifying modules strains, compared to five bovine strains (C-type). Sequence predicted would produce tripeptide Phe-N-Methyl-Val-Ala with lipid moiety, termed lipotripeptide (L3P). Comprehensive Map S397 extracts confirmed structural formula native L3P D-Phe-N-Methyl-L-Val-L-Ala-OMe attached N-ter 20-carbon fatty chain. These data demonstrate S-type which more adapted sheep, unique lipid. There is dose-dependent effect observed on upregulation CD25+ CD8 T cells infected cows, while L5P effects were static. In contrast, demonstrated significantly stronger induction B animals L3P.