Skip to Main content Skip to Navigation
Journal articles

O-Methylation of the glycopeptidolipid acyl chain defines surface hydrophobicity of Mycobacterium abscessus and macrophage invasion

Abstract : Mycobacterium abscessus, an emerging pathogen responsible for severe lung infections in cystic fibrosis patients, displays either smooth (S) or rough (R) morphotypes. The S-to-R transition is associated with reduced levels of glycopeptidolipid (GPL) production and is correlated with increased pathogenicity in animal and human hosts. While the structure of GPL is well established, its biosynthetic pathway is incomplete. In addition, the biological functions of the distinct structural parts of this complex lipid remain elusive. Herein, the fmt gene encoding a putative O-methyltransferase was deleted in the M. abscessus S variant. Subsequent biochemical and structural analyses demonstrated that methoxylation of the fatty acyl chain of GPL was abrogated in the Δfmt mutant, and this defect was rescued upon complementation with a functional fmt gene. In contrast, the introduction of fmt derivatives mutated at residues essential for methyltransferase activity failed to complement GPL defects, indicating that fmt encodes an O-methyltransferase. Unexpectedly, phenotypic analyses showed that Δfmt was more hydrophilic than its parental progenitor, as demonstrated by hexadecane-aqueous buffer partitioning and atomic force microscopy experiments with hydrophobic probes. Importantly, the invasion rate of THP-1 macrophages by Δfmt was reduced by 50% when compared to the wild-type strain. Together, these results indicate that Fmt O-methylates the lipid moiety of GPL and plays a substantial role in conditioning the surface hydrophobicity of M. abscessus as well as in the early steps of the interaction between the bacilli and macrophages.
Document type :
Journal articles
Complete list of metadata

Cited literature [62 references]  Display  Hide  Download
Contributor : Laurent Kremer Connect in order to contact the contributor
Submitted on : Monday, October 19, 2020 - 6:15:18 PM
Last modification on : Friday, August 5, 2022 - 10:58:10 AM
Long-term archiving on: : Wednesday, January 20, 2021 - 7:25:45 PM




Wassim Daher, Louis-David Leclercq, Albertus Viljoen, Jona Karam, Yves F Dufrêne, et al.. O-Methylation of the glycopeptidolipid acyl chain defines surface hydrophobicity of Mycobacterium abscessus and macrophage invasion. ACS Infectious Diseases, American Chemical Society, 2020, 6 (10), pp.2756-2770. ⟨10.1021/acsinfecdis.0c00490⟩. ⟨inserm-02971852⟩



Record views


Files downloads