Genome Mining and Chemistry-Driven Discovery of a Cell Wall Lipopeptide Signature forsubsp.Ancestral Lineage.

Abstract

subsp.() causes Johne's disease (JD), a chronic infection responsible for considerable economic losses to dairy industries worldwide. Genetically clonal,has evolved into three distinct genetic lineages designated CII, for bovine strains, and SI and SIII, for ovine strains. Previous studies have established thatdoes not produce glycopeptidolipids, characteristic of the cell wall surface of mycobacteria belonging to thecomplex, but rather sugar-free lipopeptide compounds synthesized by nonribosomal peptide synthetases. In this study, we combined genomic, machine learning, (bio)chemical, and analytical approaches to identify the metabolites biosynthesized by NRPS in the most ancestral SI strains of. We thus characterized a lipotripeptide (L3P-2) signature for the SI genetic lineage, demonstrating that the evolution of thissubspecies has been accompanied by a diversification of the cell wall lipopeptides. Finally, L3P-2 shows promise for improved serological diagnosis of JD.