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Found 4 records.
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1. (CSDB ID: 7368) | report error |
| -2)-b-D-Manp-(1- | Show graphically |
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Leishmania
(NCBI TaxID 5658,
species name lookup)
]
unimelb.edu.auParasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. The seven MTPs catalyze the constitutive synthesis and turnover of mannogen. This metabolic rheostat protects obligate intracellular parasite stages from nutrient excess, and is essential for thermotolerance and parasite infectivity in the mammalian host. Our results suggest that the acquisition and expansion of the MTP family in Leishmania increased the metabolic flexibility of these protists and contributed to their capacity to colonize new host niches.
glycosyltransferase, mannan, X-ray crystallography, carbohydrate reserve, central carbon metabolism, glycan phosphorylase, GT 108, horizontal gene transfer, parasite pathogenesis
Structure type: homopolymer ; n=2-60|
2. (CSDB ID: 20280) | report error |
| a-L-Rhap3Me4Me-(1-1)-+ | a-L-6dTalp3Ac4Ac-(1-3)-+ | | | LIP-(1-2)-D-Phe-(1-2)-D-aThr-(1-2)-D-Ala-(1-2)-Subst Subst = alaninol = SMILES N{2}C(C){1}CO | Show graphically |
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Mycobacterium abscessus
(NCBI TaxID 36809,
species name lookup)
]univ-lille.fr>; L. Kremer <laurent.kremeririm.cnrs.fr>Mycobacterium abscessus causes severe lung infections. Clinical isolates can have either smooth (S) or rough (R) colony morphotypes; of these, S but not R variants have abundant cell wall glycopeptidolipids (GPL) consisting of a peptidolipid core substituted by a 6-deoxy-α-L-talose (6-dTal) and rhamnose residues. Deletion of gtf1, encoding the 6-dTal transferase, results in the S-to-R transition, mycobacterial cord formation, and increased virulence, underscoring the importance of 6-dTal in infection outcomes. However, since 6-dTal is di-O-acetylated, it is unclear whether the gtf1 mutant phenotypes are related to the loss of the 6-dTal or the result of the absence of acetylation. Here, we addressed whether M. abscessus atf1 and atf2, encoding two putative O-acetyltransferases located within the gpl biosynthetic locus, transfer acetyl groups to 6-dTal. We found deletion of atf1 and/or atf2 did not drastically alter the GPL acetylation profile, suggesting there are additional enzymes with redundant functions. We subsequently identified two paralogs of atf1 and atf2, MAB_1725c and MAB_3448. While deletion of MAB_1725c and MAB_3448 had no effect on GPL acetylation, the triple atf1-atf2-MAB_1725c mutant did not synthetize fully acetylated GPL, and the quadruple mutant was totally devoid of acetylated GPL. Moreover, both triple and quadruple mutants accumulated hyper-methylated GPL. Finally, we show deletion of atf genes resulted in subtle changes in colony morphology but had no effect on M. abscessus internalization by macrophages. Overall, these findings reveal the existence of functionally redundant O-acetyltransferases and suggest that O-acetylation influences the glycan moiety of GPL by deflecting biosynthetic flux in M. abscessus.
cell wall, mass spectrometry, glycopeptidolipid, acetyltransferase, macrophage, Mycobacterium abscessus
Structure type: oligomer|
3. (CSDB ID: 22248) | report error |
| a-L-Rhap-(1-2)-a-L-Rhap3Me4Me-(1-1)-+ | a-L-6dTalp3Ac4Ac-(1-3)-+ | | | LIP-(1-2)-D-Phe-(1-2)-D-aThr-(1-2)-D-Ala-(1-2)-Subst Subst = alaninol = SMILES N{2}C(C){1}CO | Show graphically |
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Mycobacterium abscessus
(NCBI TaxID 36809,
species name lookup)
Mycobacterium smegmatis
(NCBI TaxID 1772,
species name lookup)
]univ-lille.fr>; L. Kremer <laurent.kremeririm.cnrs.fr>Mycobacterium abscessus causes severe lung infections. Clinical isolates can have either smooth (S) or rough (R) colony morphotypes; of these, S but not R variants have abundant cell wall glycopeptidolipids (GPL) consisting of a peptidolipid core substituted by a 6-deoxy-α-L-talose (6-dTal) and rhamnose residues. Deletion of gtf1, encoding the 6-dTal transferase, results in the S-to-R transition, mycobacterial cord formation, and increased virulence, underscoring the importance of 6-dTal in infection outcomes. However, since 6-dTal is di-O-acetylated, it is unclear whether the gtf1 mutant phenotypes are related to the loss of the 6-dTal or the result of the absence of acetylation. Here, we addressed whether M. abscessus atf1 and atf2, encoding two putative O-acetyltransferases located within the gpl biosynthetic locus, transfer acetyl groups to 6-dTal. We found deletion of atf1 and/or atf2 did not drastically alter the GPL acetylation profile, suggesting there are additional enzymes with redundant functions. We subsequently identified two paralogs of atf1 and atf2, MAB_1725c and MAB_3448. While deletion of MAB_1725c and MAB_3448 had no effect on GPL acetylation, the triple atf1-atf2-MAB_1725c mutant did not synthetize fully acetylated GPL, and the quadruple mutant was totally devoid of acetylated GPL. Moreover, both triple and quadruple mutants accumulated hyper-methylated GPL. Finally, we show deletion of atf genes resulted in subtle changes in colony morphology but had no effect on M. abscessus internalization by macrophages. Overall, these findings reveal the existence of functionally redundant O-acetyltransferases and suggest that O-acetylation influences the glycan moiety of GPL by deflecting biosynthetic flux in M. abscessus.
cell wall, mass spectrometry, glycopeptidolipid, acetyltransferase, macrophage, Mycobacterium abscessus
Structure type: oligomer|
4. (CSDB ID: 32085) | report error |
| a-L-Rhap-(1-2)-a-L-Rhap3Me4Me-(1-1)-+ | a-L-6dTalp3Ac4Ac-(1-3)-+ | | | LIP-(1-2)-D-Phe-(1-2)-D-aThr-(1-2)-D-Ala-(1-2)-Subst Subst = alaninol = SMILES N{2}C(C){1}CO | Show graphically |
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Mycobacterium abscessus CIP104536(T)
(Ancestor NCBI TaxID 36809,
species name lookup)
]irim.cnrs.frMycobacterium 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.
glycopeptidolipid, phagocytosis, atomic force microscopy, hydrophobicity, Mycobacterium abscessus, O-methyltransferase
Structure type: oligomer| New query | Export IDs | Home | Help |
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