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Genome Mining and Chemistry-Driven Discovery of a Cell Wall Lipopeptide Signature for Mycobacterium avium subsp. paratuberculosis Ancestral Lineage

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Title: Genome Mining and Chemistry-Driven Discovery of a Cell Wall Lipopeptide Signature for Mycobacterium avium subsp. paratuberculosis Ancestral Lineage
Authors: Bannantine, John, Etienne, Gilles, Lemassu, Anne, Cochard, Thierry, Ganneau, Christelle, Melo, Sandrine, Conde, Cyril, Marrakchi, Hedia, Bay, Sylvie, Biet, Franck
Contributors: Lassailly-Bondaz, Anne
Source: ACS Infectious Diseases. 11:1635-1647
Publisher Information: American Chemical Society (ACS), 2025.
Publication Year: 2025
Subject Terms: Mycobacterium avium subsp. paratuberculosis, Johne's Disease, Diagnosis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Non-Ribosomal Peptide Synthetases, GlycoPeptidoLipids, Lipopeptide
Description: Mycobacterium avium subsp. paratuberculosis (Map) causes Johne's disease (JD), a chronic infection responsible for considerable economic losses to dairy industries worldwide. Genetically clonal, Map has evolved into three distinct genetic lineages designated CII, for bovine strains, and SI and SIII, for ovine strains. Previous studies have established that Map does not produce glycopeptidolipids, characteristic of the cell wall surface of mycobacteria belonging to the M. avium complex, 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 Map. We thus characterized a lipotripeptide (L3P-2) signature for the SI genetic lineage, demonstrating that the evolution of this Map subspecies has been accompanied by a diversification of the cell wall lipopeptides. Finally, L3P-2 shows promise for improved serological diagnosis of JD.
Document Type: Article
File Description: application/pdf
Language: English
ISSN: 2373-8227
DOI: 10.1021/acsinfecdis.5c00181
Access URL: https://pubmed.ncbi.nlm.nih.gov/40397513
https://pasteur.hal.science/pasteur-05078870v1
https://pasteur.hal.science/pasteur-05078870v1/document
https://doi.org/10.1021/acsinfecdis.5c00181
Rights: STM Policy #29
CC BY
Accession Number: edsair.doi.dedup.....a46d4de0f79fe01bdf0ed494138182f9
Database: OpenAIRE
Description
Abstract:Mycobacterium avium subsp. paratuberculosis (Map) causes Johne's disease (JD), a chronic infection responsible for considerable economic losses to dairy industries worldwide. Genetically clonal, Map has evolved into three distinct genetic lineages designated CII, for bovine strains, and SI and SIII, for ovine strains. Previous studies have established that Map does not produce glycopeptidolipids, characteristic of the cell wall surface of mycobacteria belonging to the M. avium complex, 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 Map. We thus characterized a lipotripeptide (L3P-2) signature for the SI genetic lineage, demonstrating that the evolution of this Map subspecies has been accompanied by a diversification of the cell wall lipopeptides. Finally, L3P-2 shows promise for improved serological diagnosis of JD.
ISSN:23738227
DOI:10.1021/acsinfecdis.5c00181