Journal Article

Lipopentapeptide induces a strong host humoral response and distinguishesMycobacterium aviumsubsp.paratuberculosisfromM. aviumsubsp.avium

Gokhale, Rajesh, Bay, Sylvie, Thibault, Virginie C, Biet, Franck, Euphrasie, Daniel, Ganneau, Christelle, Daffé, Mamadou, Grayon, Maggy, Etienne, Gilles, Reyrat, Jean-Marc, Lanotte, Philippe

2008

Overview

Background Many non-tuberculous mycobacteria synthesize abundant glycopeptidolipids (GPLs). These surface-located GPLs are involved in pathogenicity by interfering with the host immune system. InMycobacterium aviumsubsp.avium(Mav), GPLs consist of a lipopeptide core composed of a tetrapeptideO-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 theMavisolates produce GPLs, the picture is not as clear forM.aviumsubsp.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 characterizedMapisolates showed that allMapstrains tested produce a lipopentapeptide (L5P) instead of GPLs. To provide a genomic basis for the synthesis of this compound, the recently published genome sequence ofMapwas explored usingin silicomethods. Even thoughMapproduces a lipopeptide rather than GPL, its genome contains nevertheless a locus highly similar to the GPL biosynthetic pathway ofMav.We showed that the module composition of the non-ribosomal protein synthase (Nrp) ofMap, the enzyme involved in the synthesis of the peptidyl moiety, is dramatically different from that of other GPL producers such asM. smegmatis(Ms) andMavand 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 inMapinfected animals. Conclusions These genomic and biochemical differences may help to unambiguously distinguishMapfromMavand also fromM. bovis, to reclassify related strains of theMapspecies and to allow the convenient and specific diagnosis of paratuberculosis.

• Publisher: Elsevier Limited
• Subject: Amino acids / Bacteriology / Biochemical analysis / Biosynthesis / Chromatography / Genomics / Immune system / Lipids / Mass spectrometry / Pathogens / Saccharides