PUBLICATION
A dTDP-L-Rhamnose 4-epimerase required for glycopeptidolipid biosynthesis in Mycobacterium abscessus
- Authors
- Aguilera-Correa, J.J., Wei, F., Leclercq, L.D., Tasrini, Y., Mullapudi, E., Daher, W., Nakajima, K., Canaan, S., Herrmann, J.L., Wilmanns, M., Guérardel, Y., Wen, L., Kremer, L.
- ID
- ZDB-PUB-241004-11
- Date
- 2024
- Source
- The Journal of biological chemistry 300(11): 107852 (Journal)
- Registered Authors
- Tasrini, Yara
- Keywords
- 6-deoxy-Talose, Mycobacterium abscessus, cell wall, Rhamnose, epimerase, glycopeptidolipid, morphotype, virulence, zebrafish.
- MeSH Terms
-
- Bacterial Proteins*/genetics
- Bacterial Proteins*/metabolism
- Humans
- Nucleoside Diphosphate Sugars/biosynthesis
- Nucleoside Diphosphate Sugars/metabolism
- Deoxy Sugars/biosynthesis
- Deoxy Sugars/metabolism
- Rhamnose/biosynthesis
- Rhamnose/metabolism
- Virulence
- Biofilms/growth & development
- Animals
- Carbohydrate Epimerases/genetics
- Carbohydrate Epimerases/metabolism
- Zebrafish*
- Glycolipids*/biosynthesis
- Glycolipids*/metabolism
- Glycopeptides/biosynthesis
- Glycopeptides/metabolism
- Racemases and Epimerases/genetics
- Racemases and Epimerases/metabolism
- Hexoses
- Mycobacterium abscessus*/enzymology
- Mycobacterium abscessus*/genetics
- Mycobacterium abscessus*/metabolism
- Mycobacterium Infections, Nontuberculous/microbiology
- Thymine Nucleotides/metabolism
- PubMed
- 39362472 Full text @ J. Biol. Chem.
Citation
Aguilera-Correa, J.J., Wei, F., Leclercq, L.D., Tasrini, Y., Mullapudi, E., Daher, W., Nakajima, K., Canaan, S., Herrmann, J.L., Wilmanns, M., Guérardel, Y., Wen, L., Kremer, L. (2024) A dTDP-L-Rhamnose 4-epimerase required for glycopeptidolipid biosynthesis in Mycobacterium abscessus. The Journal of biological chemistry. 300(11):107852.
Abstract
Mycobacterium abscessus causes severe lung infections in cystic fibrosis patients and exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in the S-to-R transition but the underlying molecular mechanisms of this transition remain incompletely understood. Herein, we characterized MAB_4111c in relation to GPL synthesis and investigated the effects of MAB_4111c deletion in M. abscessus pathogenicity. An enzymatic assay indicated that MAB_4111c, also designated Tle for Talose epimerase, is converting dTDP-L-Rhamnose into dTDP-6-deoxy-L-Talose. A tle deletion mutant was constructed in the S variant of M. abscessus and relative areas of Rhamnose and 6-deoxy-Talose and their methylated forms expressed as ratios of total monosaccharides, showed an altered GPL profile lacking 6-deoxy-Talose. Thus, Tle provides dTDP-6-deoxy-L-Talose, subsequently used by the glycosyltransferase Gtf1 to transfer 6-deoxy-Talose to the GPL backbone. Strikingly, the tle mutant exhibited a R morphotype, showed impaired sliding motility and biofilm formation, and these phenotypes were rescued upon functional complementation. Moreover, deletion of tle in M. abscessus results in increased pathogenicity and killing in zebrafish embryos. Together, our results underscore the importance of the dTDP-L-Rhamnose 4-epimerase activity in GPL biosynthesis and in influencing M. abscessus virulence.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping