Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan

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Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan. / Driessen, NN; Stoop, EJM; Ummels, R; Gurcha, Sudagar; Mishra, Arun Kumar; Larrouy-Maumus, G; Nigou, J; Gilleron, M; Puzo, G; Maaskant, JJ; Sparrius, M; Besra, Gurdyal; Bitter, W; Vandenbroucke-Grauls, CMJE; Appelmelk, BJ.

In: Microbiology, Vol. 156, 01.11.2010, p. 3492-3502.

Research output: Contribution to journalArticlepeer-review

Harvard

Driessen, NN, Stoop, EJM, Ummels, R, Gurcha, S, Mishra, AK, Larrouy-Maumus, G, Nigou, J, Gilleron, M, Puzo, G, Maaskant, JJ, Sparrius, M, Besra, G, Bitter, W, Vandenbroucke-Grauls, CMJE & Appelmelk, BJ 2010, 'Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan', Microbiology, vol. 156, pp. 3492-3502. https://doi.org/10.1099/mic.0.037507-0

APA

Driessen, NN., Stoop, EJM., Ummels, R., Gurcha, S., Mishra, A. K., Larrouy-Maumus, G., Nigou, J., Gilleron, M., Puzo, G., Maaskant, JJ., Sparrius, M., Besra, G., Bitter, W., Vandenbroucke-Grauls, CMJE., & Appelmelk, BJ. (2010). Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan. Microbiology, 156, 3492-3502. https://doi.org/10.1099/mic.0.037507-0

Vancouver

Author

Driessen, NN ; Stoop, EJM ; Ummels, R ; Gurcha, Sudagar ; Mishra, Arun Kumar ; Larrouy-Maumus, G ; Nigou, J ; Gilleron, M ; Puzo, G ; Maaskant, JJ ; Sparrius, M ; Besra, Gurdyal ; Bitter, W ; Vandenbroucke-Grauls, CMJE ; Appelmelk, BJ. / Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan. In: Microbiology. 2010 ; Vol. 156. pp. 3492-3502.

Bibtex

@article{b2da41ac49894039b650d2047db5e745,
title = "Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan",
abstract = "Lipoarabinomannan (LAM) is a major glycolipid in the mycobacterial cell envelope. LAM consists of a mannosylphosphatidylinositol (MPI) anchor, a mannan core and a branched arabinan domain. The termini of the arabinan branches can become substituted with one to three alpha(1 -> 2)-linked mannosyl residues, the mannose cap, producing ManLAM. ManLAM has been associated with a range of different immunomodulatory properties of Mycobacterium tuberculosis during infection of the host. In some of these effects, the presence of the mannose cap on ManLAM appears to be crucial for its activity. So far, in the biosynthesis of the mannose cap on ManLAM, two enzymes have been reported to be involved: a mannosyltransferase that adds the first mannosyl residue of the mannose caps to the arabinan domain of LAM, and another mannosyltransferase that elongates the mannose cap up to three mannosyl residues. Here, we report that a third gene is involved, MMAR_2380, which is the Mycobacterium marinum orthologue of Rv1565c. MMAR_2380 encodes a predicted transmembrane acyltransferase. In M. marinum Delta MMAR_2380, the LAM arabinan domain is still intact, but the mutant LAM lacks the mannose cap. Additional effects of mutation of MMAR_2380 on LAM were observed: a higher degree of branching of both the arabinan domain and the mannan core, and a decreased incorporation of [1,2-C-14]acetate into the acyl chains in mutant LAM as compared with the wild-type form. This latter effect was also observed for related lipoglycans, i.e. lipomannan (LM) and phosphatidylinositol mannosides (PIMs). Furthermore, the mutant strain showed increased aggregation in liquid cultures as compared with the wild-type strain. All phenotypic traits of M. marinum Delta MMAR_2380, the deficiency in the mannose cap on LAM and changes at the cell surface, could be reversed by complementing the mutant strain with MMAR_2380. Strikingly, membrane preparations of the mutant strain still showed enzymic activity for the arabinan mannose-capping mannosyltransferase similar to that of the wild-type strain. Although the exact function of MMAR_2380 remains unknown, we show that the protein is essential for the presence of a mannose cap on LAM.",
author = "NN Driessen and EJM Stoop and R Ummels and Sudagar Gurcha and Mishra, {Arun Kumar} and G Larrouy-Maumus and J Nigou and M Gilleron and G Puzo and JJ Maaskant and M Sparrius and Gurdyal Besra and W Bitter and CMJE Vandenbroucke-Grauls and BJ Appelmelk",
year = "2010",
month = nov,
day = "1",
doi = "10.1099/mic.0.037507-0",
language = "English",
volume = "156",
pages = "3492--3502",
journal = "Microbiology",
issn = "1350-0872",
publisher = "Society for General Microbiology",

}

RIS

TY - JOUR

T1 - Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan

AU - Driessen, NN

AU - Stoop, EJM

AU - Ummels, R

AU - Gurcha, Sudagar

AU - Mishra, Arun Kumar

AU - Larrouy-Maumus, G

AU - Nigou, J

AU - Gilleron, M

AU - Puzo, G

AU - Maaskant, JJ

AU - Sparrius, M

AU - Besra, Gurdyal

AU - Bitter, W

AU - Vandenbroucke-Grauls, CMJE

AU - Appelmelk, BJ

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Lipoarabinomannan (LAM) is a major glycolipid in the mycobacterial cell envelope. LAM consists of a mannosylphosphatidylinositol (MPI) anchor, a mannan core and a branched arabinan domain. The termini of the arabinan branches can become substituted with one to three alpha(1 -> 2)-linked mannosyl residues, the mannose cap, producing ManLAM. ManLAM has been associated with a range of different immunomodulatory properties of Mycobacterium tuberculosis during infection of the host. In some of these effects, the presence of the mannose cap on ManLAM appears to be crucial for its activity. So far, in the biosynthesis of the mannose cap on ManLAM, two enzymes have been reported to be involved: a mannosyltransferase that adds the first mannosyl residue of the mannose caps to the arabinan domain of LAM, and another mannosyltransferase that elongates the mannose cap up to three mannosyl residues. Here, we report that a third gene is involved, MMAR_2380, which is the Mycobacterium marinum orthologue of Rv1565c. MMAR_2380 encodes a predicted transmembrane acyltransferase. In M. marinum Delta MMAR_2380, the LAM arabinan domain is still intact, but the mutant LAM lacks the mannose cap. Additional effects of mutation of MMAR_2380 on LAM were observed: a higher degree of branching of both the arabinan domain and the mannan core, and a decreased incorporation of [1,2-C-14]acetate into the acyl chains in mutant LAM as compared with the wild-type form. This latter effect was also observed for related lipoglycans, i.e. lipomannan (LM) and phosphatidylinositol mannosides (PIMs). Furthermore, the mutant strain showed increased aggregation in liquid cultures as compared with the wild-type strain. All phenotypic traits of M. marinum Delta MMAR_2380, the deficiency in the mannose cap on LAM and changes at the cell surface, could be reversed by complementing the mutant strain with MMAR_2380. Strikingly, membrane preparations of the mutant strain still showed enzymic activity for the arabinan mannose-capping mannosyltransferase similar to that of the wild-type strain. Although the exact function of MMAR_2380 remains unknown, we show that the protein is essential for the presence of a mannose cap on LAM.

AB - Lipoarabinomannan (LAM) is a major glycolipid in the mycobacterial cell envelope. LAM consists of a mannosylphosphatidylinositol (MPI) anchor, a mannan core and a branched arabinan domain. The termini of the arabinan branches can become substituted with one to three alpha(1 -> 2)-linked mannosyl residues, the mannose cap, producing ManLAM. ManLAM has been associated with a range of different immunomodulatory properties of Mycobacterium tuberculosis during infection of the host. In some of these effects, the presence of the mannose cap on ManLAM appears to be crucial for its activity. So far, in the biosynthesis of the mannose cap on ManLAM, two enzymes have been reported to be involved: a mannosyltransferase that adds the first mannosyl residue of the mannose caps to the arabinan domain of LAM, and another mannosyltransferase that elongates the mannose cap up to three mannosyl residues. Here, we report that a third gene is involved, MMAR_2380, which is the Mycobacterium marinum orthologue of Rv1565c. MMAR_2380 encodes a predicted transmembrane acyltransferase. In M. marinum Delta MMAR_2380, the LAM arabinan domain is still intact, but the mutant LAM lacks the mannose cap. Additional effects of mutation of MMAR_2380 on LAM were observed: a higher degree of branching of both the arabinan domain and the mannan core, and a decreased incorporation of [1,2-C-14]acetate into the acyl chains in mutant LAM as compared with the wild-type form. This latter effect was also observed for related lipoglycans, i.e. lipomannan (LM) and phosphatidylinositol mannosides (PIMs). Furthermore, the mutant strain showed increased aggregation in liquid cultures as compared with the wild-type strain. All phenotypic traits of M. marinum Delta MMAR_2380, the deficiency in the mannose cap on LAM and changes at the cell surface, could be reversed by complementing the mutant strain with MMAR_2380. Strikingly, membrane preparations of the mutant strain still showed enzymic activity for the arabinan mannose-capping mannosyltransferase similar to that of the wild-type strain. Although the exact function of MMAR_2380 remains unknown, we show that the protein is essential for the presence of a mannose cap on LAM.

U2 - 10.1099/mic.0.037507-0

DO - 10.1099/mic.0.037507-0

M3 - Article

C2 - 20688818

VL - 156

SP - 3492

EP - 3502

JO - Microbiology

JF - Microbiology

SN - 1350-0872

ER -