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

IF 3.8 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2025-06-13 Epub Date: 2025-05-21 DOI:10.1021/acsinfecdis.5c00181

John P Bannantine, Gilles Etienne, Anne Lemassu, Thierry Cochard, Christelle Ganneau, Sandrine Melo, Cyril Conde, Hedia Marrakchi, Sylvie Bay, Franck Biet

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引用次数: 0

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.

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禽分枝杆菌亚种细胞壁脂肽特征的基因组挖掘和化学驱动发现。副结核的祖先血统。

鸟分枝杆菌亚种副结核（Map）引起约翰氏病（JD），这是一种慢性感染，对全球乳制品行业造成相当大的经济损失。遗传克隆，Map已经进化成三个不同的遗传谱系，分别为牛株的CII和羊株的SI和SIII。先前的研究已经证实，Map并不产生属于M. avium复合体的分枝杆菌细胞壁表面特有的糖肽类脂质，而是由非核糖体肽合成酶合成的无糖脂肽化合物。在这项研究中，我们结合了基因组学、机器学习、（生物）化学和分析方法，鉴定了大多数Map祖先SI菌株中NRPS生物合成的代谢物。因此，我们表征了SI遗传谱系的脂三肽（L3P-2）特征，表明该Map亚种的进化伴随着细胞壁脂肽的多样化。最后，L3P-2有望改善JD的血清学诊断。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.