Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides

Rebecca J. Edgar; Vincent P. van Hensbergen; Alessandro Ruda; Andrew G. Turner; Pan Deng; Yoann le Breton; Najib M. el-Sayed; Ashton T. Belew; Kevin S. McIver; Alastair G. McEwan; Andrew J. Morris; G. rard Lambeau; Mark J. Walker; Jeffrey S. Rush; Konstantin V. Korotkov; G. ran Widmalm; Nina M. van Sorge; Natalia Korotkova

doi:https://doi.org/10.1038/s41589-019-0251-4

Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides

Rebecca J. Edgar, Vincent P. van Hensbergen, Alessandro Ruda, Andrew G. Turner, Pan Deng, Yoann le Breton, Najib M. el-Sayed, Ashton T. Belew, Kevin S. McIver, Alastair G. McEwan, Andrew J. Morris, G. rard Lambeau, Mark J. Walker, Jeffrey S. Rush, Konstantin V. Korotkov, G. ran Widmalm, Nina M. van Sorge, Natalia Korotkova

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Abstract

Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A 2 . Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host–pathogen interaction and has implications for vaccine design.

Original language	English
Pages (from-to)	463-471
Journal	Nature chemical biology
Volume	15
Issue number	5
DOIs	https://doi.org/10.1038/s41589-019-0251-4
Publication status	Published - 1 May 2019
Externally published	Yes

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https://doi.org/10.1038/s41589-019-0251-4

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470023

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Edgar, R. J., van Hensbergen, V. P., Ruda, A., Turner, A. G., Deng, P., le Breton, Y., el-Sayed, N. M., Belew, A. T., McIver, K. S., McEwan, A. G., Morris, A. J., Lambeau, G. R., Walker, M. J., Rush, J. S., Korotkov, K. V., Widmalm, G. R., van Sorge, N. M., & Korotkova, N. (2019). Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides. Nature chemical biology, 15(5), 463-471. https://doi.org/10.1038/s41589-019-0251-4

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title = "Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides",

abstract = "Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A 2 . Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host–pathogen interaction and has implications for vaccine design.",

author = "Edgar, {Rebecca J.} and {van Hensbergen}, {Vincent P.} and Alessandro Ruda and Turner, {Andrew G.} and Pan Deng and {le Breton}, Yoann and el-Sayed, {Najib M.} and Belew, {Ashton T.} and McIver, {Kevin S.} and McEwan, {Alastair G.} and Morris, {Andrew J.} and Lambeau, {G. rard} and Walker, {Mark J.} and Rush, {Jeffrey S.} and Korotkov, {Konstantin V.} and Widmalm, {G. ran} and {van Sorge}, {Nina M.} and Natalia Korotkova",

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doi = "https://doi.org/10.1038/s41589-019-0251-4",

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Edgar, RJ, van Hensbergen, VP, Ruda, A, Turner, AG, Deng, P, le Breton, Y, el-Sayed, NM, Belew, AT, McIver, KS, McEwan, AG, Morris, AJ, Lambeau, GR, Walker, MJ, Rush, JS, Korotkov, KV, Widmalm, GR, van Sorge, NM & Korotkova, N 2019, 'Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides', Nature chemical biology, vol. 15, no. 5, pp. 463-471. https://doi.org/10.1038/s41589-019-0251-4

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T1 - Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides

AU - Edgar, Rebecca J.

AU - van Hensbergen, Vincent P.

AU - Ruda, Alessandro

AU - Turner, Andrew G.

AU - Deng, Pan

AU - le Breton, Yoann

AU - el-Sayed, Najib M.

AU - Belew, Ashton T.

AU - McIver, Kevin S.

AU - McEwan, Alastair G.

AU - Morris, Andrew J.

AU - Lambeau, G. rard

AU - Walker, Mark J.

AU - Rush, Jeffrey S.

AU - Korotkov, Konstantin V.

AU - Widmalm, G. ran

AU - van Sorge, Nina M.

AU - Korotkova, Natalia

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A 2 . Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host–pathogen interaction and has implications for vaccine design.

AB - Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A 2 . Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host–pathogen interaction and has implications for vaccine design.

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VL - 15

SP - 463

EP - 471

JO - Nature chemical biology

JF - Nature chemical biology

IS - 5

ER -

Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides

Abstract

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