ArticleProceedings of the National Academy of Sciences of the United States of America2016
Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 81 citations in OpenAlex.
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- An enoyl-ACP reductase inhibitor, NITD-916, expresses anti-Antimicrobial agents and chemotherapy · 2025Article
- A glycosylated lipooctapeptide promotes uptake and growth of Mycobacterium abscessus in the host.Nature communications · 2025Article
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- Lipoarabinomannan modification as a source of phenotypic heterogeneity in host-adaptedProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Targeted Chromosomal Barcoding Establishes Direct Genotype-Phenotype Associations for Antibiotic Resistance in Mycobacterium abscessus.Microbiology spectrum · 2023Article
- DS86760016, a Leucyl-tRNA Synthetase Inhibitor, Is Active against Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2023Article
- The cell envelope of Mycobacterium abscessus and its role in pathogenesis.PLoS pathogens · 2023Review
- A Genome-Wide Screen in Macrophages Defines Host Genes Regulating the Uptake of Mycobacterium abscessus.mSphere · 2023Article
- Review
- Calcium carbonate mineralization is essential for biofilm formation and lung colonization.iScience · 2022Article
- Rough and smooth variants of Mycobacterium abscessus are differentially controlled by host immunity during chronic infection of adult zebrafish.Nature communications · 2022Article
- Mycobacterial Adhesion: From Hydrophobic to Receptor-Ligand Interactions.Microorganisms · 2022Review
- Virulence Mechanisms ofFrontiers in microbiology · 2022Review
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12 authors at 9 institutions in 2 countries.
Funding
Abstract
Mycobacterium abscessus (Mabs) is a rapidly growing Mycobacterium and an emerging pathogen in humans. Transitioning from a smooth (S) high-glycopeptidolipid (GPL) producer to a rough (R) low-GPL producer is associated with increased virulence in zebrafish, which involves the formation of massive serpentine cords, abscesses, and rapid larval death. Generating a cord-deficient Mabs mutant would allow us to address the contribution of cording in the physiopathological signs of the R variant. Herein, a deletion mutant of MAB_4780, encoding a dehydratase, distinct from the β-hydroxyacyl-ACP dehydratase HadABC complex, was constructed in the R morphotype. This mutant exhibited an alteration of the mycolic acid composition and a pronounced defect in cording. This correlated with an extremely attenuated phenotype not only in wild-type but also in immunocompromised zebrafish embryos lacking either macrophages or neutrophils. The abolition of granuloma formation in embryos infected with the dehydratase mutant was associated with a failure to replicate in macrophages, presumably due to limited inhibition of the phagolysosomal fusion. Overall, these results indicate that MAB_4780 is required for Mabs to successfully establish acute and lethal infections. Therefore, targeting MAB_4780 may represent an attractive antivirulence strategy to control Mabs infections, refractory to most standard chemotherapeutic interventions. The combination of a dehydratase assay with a high-resolution crystal structure of MAB_4780 opens the way to identify such specific inhibitors.
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