PUBLICATION
Glycopeptidolipid glycosylation controls surface properties and pathogenicity in Mycobacterium abscessus
- Authors
- Daher, W., Leclercq, L.D., Johansen, M.D., Hamela, C., Karam, J., Trivelli, X., Nigou, J., Guérardel, Y., Kremer, L.
- ID
- ZDB-PUB-220401-14
- Date
- 2022
- Source
- Cell chemical biology 29(5): 910-924.e7 (Journal)
- Registered Authors
- Keywords
- Mycobacterium abscessus, glycopeptidolipid, glycosyltransferase, internalization, macrophage, mannose receptor, morphotype, rhamnose, virulence, zebrafish
- MeSH Terms
-
- Glycosylation
- Virulence
- Zebrafish
- Surface Properties
- Animals
- Rhamnose
- Mycobacterium abscessus*
- PubMed
- 35358417 Full text @ Cell Chem Biol
Citation
Daher, W., Leclercq, L.D., Johansen, M.D., Hamela, C., Karam, J., Trivelli, X., Nigou, J., Guérardel, Y., Kremer, L. (2022) Glycopeptidolipid glycosylation controls surface properties and pathogenicity in Mycobacterium abscessus. Cell chemical biology. 29(5):910-924.e7.
Abstract
Mycobacterium abscessus is an emerging and difficult-to-manage mycobacterial species that exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in transition from S to R and severe lung disease. A structure-activity relationship study was undertaken to decipher the role of GPL glycosylation in morphotype transition and pathogenesis. Deletion of gtf3 uncovered the prominent role of the extra rhamnose in enhancing mannose receptor-mediated internalization of M. abscessus by macrophages. In contrast, the absence of the 6-deoxy-talose and the first rhamnose in mutants lacking gtf1 and gtf2, respectively, affected M abscessus phagocytosis but also resulted in the S-to-R transition. Strikingly, gtf1 and gtf2 mutants displayed a strong propensity to form cords and abscesses in zebrafish, leading to robust and lethal infection. Together, these results underscore the importance and differential contribution of GPL monosaccharides in promoting virulence and infection outcomes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping