title: Lipopentapeptide induces a strong host humoral response and distinguishes Mycobacterium avium subsp. paratuberculosis from M. avium subsp. avium.
abstract: BACKGROUND
  Many non-tuberculous mycobacteria synthesize abundant glycopeptidolipids (GPLs). These surface-located GPLs are involved in pathogenicity by interfering with the host immune system. In Mycobacterium avium subsp. avium (Mav), GPLs consist of a lipopeptide core composed of a tetrapeptide O-linked to mono- and oligo-saccharides. The biosynthesis pathway of the simplest GPLs is now relatively well understood and involves probably more than fifteen genes. Whereas it is very obvious that most, if not all, of the Mav isolates produce GPLs, the picture is not as clear for M. avium subsp. paratuberculosis (Map), the etiologic agent of Johne's disease in cattle, and several conflicting data have been produced.
  
  
  METHODS
  Biochemical analysis of a large set of characterized Map isolates showed that all Map strains tested produce a lipopentapeptide (L5P) instead of GPLs. To provide a genomic basis for the synthesis of this compound, the recently published genome sequence of Map was explored using in silico methods. Even though Map produces a lipopeptide rather than GPL, its genome contains nevertheless a locus highly similar to the GPL biosynthetic pathway of Mav. We showed that the module composition of the non-ribosomal protein synthase (Nrp) of Map, the enzyme involved in the synthesis of the peptidyl moiety, is dramatically different from that of other GPL producers such as M. smegmatis (Ms) and Mav and is in agreement with the amino acid content of the L5P. We also showed that the peptidyl moiety of the L5P is a target for a strong specific humoral response in Map infected animals.
  
  
  CONCLUSIONS
  These genomic and biochemical differences may help to unambiguously distinguish Map from Mav and also from M. bovis, to reclassify related strains of the Map species and to allow the convenient and specific diagnosis of paratuberculosis.
authors: UR1282, Infectiologie Animale, Santé Publique, INRA centre de Tours, F-37380 Nouzilly, France.
authors: Franck
authors: F
authors: Biet
authors: Sylvie
authors: S
authors: Bay
authors: Virginie C
authors: VC
authors: Thibault
authors: Daniel
authors: D
authors: Euphrasie
authors: Maggy
authors: M
authors: Grayon
authors: Christelle
authors: C
authors: Ganneau
authors: Philippe
authors: P
authors: Lanotte
authors: Mamadou
authors: M
authors: Daffé
authors: Rajesh
authors: R
authors: Gokhale
authors: Gilles
authors: G
authors: Etienne
authors: Jean-Marc
authors: JM
authors: Reyrat
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D053898:Biosynthetic Pathways / Q000235:genetics; D002417:Cattle; D019295:Computational Biology; D004269:DNA, Bacterial / Q000235:genetics; D006017:Glycolipids / Q000032:analysis / Q000276:immunology*; D006020:Glycopeptides / Q000032:analysis / Q000276:immunology*; D009162:Mycobacterium avium / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D010283:Paratuberculosis / Q000175:diagnosis / Q000382:microbiology; D010453:Peptide Synthases / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004269:DNA, Bacterial; D006017:Glycolipids; D006020:Glycopeptides; C010762:peptidoglycolipids; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase