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 Morris; Gérard Lambeau; Mark J. Walker; Jeffrey S. Rush; Konstantin V. Korotkov; Göran Widmalm; Nina M. van Sorge; Natalia Korotkova

doi: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 Morris
, Gérard Lambeau
, Mark J. Walker
, Jeffrey S. Rush
, Konstantin V. Korotkov
, Göran Widmalm
, Nina M. van Sorge
, Natalia Korotkova

Producción científica: Article › revisión exhaustiva

59 Citas (SciVal)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	463-471
Número de páginas	9
Publicación	Nature Chemical Biology
Volumen	15
N.º	5
DOI	https://doi.org/10.1038/s41589-019-0251-4
Estado	Published - may 1 2019

Nota bibliográfica

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Financiación

This work was supported by the Center of Biomedical Research Excellence (COBRE) Pilot Grant (to N.K., K.V.K. and J.S.R.) supported by NIH grant No. P30GM110787 from the National Institute of General Medical Sciences (NIGMS); NIH grant No. R56AI135021 from the National Institute of Allergy and Infectious Diseases (NIAID) (to N.K.); VIDI grant No. 91713303 from the Netherlands Organization for Scientific Research (NWO) (to N.M.vS. and V.P.vH.); the Swedish Research Council (Nos. 2013– 4859 and 2017–03703) and The Knut and Alice Wallenberg Foundation (to G.W.); NIH grant No. P30GM127211 from the NIGMS and NIH grant No. 1S10OD021753 (to A.J.M.); the National Health and Medical Research Council of Australia (to M.J.W.); grants from CNRS, ANR (MNaims No. ANR-17-CE17-0012-01) and FRM (No. SPF20150934219) (to G.L.); NIH grant No. AI047928 from NIAID (to K.S.M. and Y.L.B.); and NIH grant No. AI094773 (to N.M.E.S. and A.T.B.). Carbohydrate composition analysis at the Complex Carbohydrate Research Center was supported by the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, US Department of Energy grant (No. DE-FG02-93ER20097) to P.A. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31–109-Eng-38 and NIH grants Nos. S10_RR25528 and S10_RR028976. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the NIH, NIGMS including No. P41GM103393. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH.

Financiadores	Número del financiador
DOE Basic Energy Sciences
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Center of Biomedical Research Excellence
National Institutes of Health (NIH)
Australian National Health and Medical Research Council
Chemical Sciences, Geosciences, and Biosciences Division
Biological and Environmental Research	P41GM103393
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	P30GM110787, P41GM103393, P30GM127211, P20GM103527
NIH Office of the Director	S10OD021753
Office of Science Programs	S10_RR028976, S10_RR25528, 109-Eng-38, DE-AC02-76SF00515
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	R01AI094773, R01AI047928, R56AI135021, 91713303
Knut och Alice Wallenbergs Stiftelse	1S10OD021753, P30GM127211
French Agence Nationale de la Recherche	ANR-17-CE17-0012
U.S. Department of Energy EPSCoR	DE-FG02-93ER20097
CNRS Centre National de la Recherche Scientifique	ANR-17-CE17-0012-01
Vetenskapsrådet	2017–03703, 2013– 4859
Fondation pour la Recherche Médicale	AI047928, AI094773, SPF20150934219

ODS de las Naciones Unidas

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ASJC Scopus subject areas

Molecular Biology
Cell Biology

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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., Lambeau, G., Walker, M. J., Rush, J. S., Korotkov, K. V., Widmalm, G., 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 Andrew Morris and G{\'e}rard Lambeau and Walker, \{Mark J.\} and Rush, \{Jeffrey S.\} and Korotkov, \{Konstantin V.\} and G{\"o}ran Widmalm and \{van Sorge\}, \{Nina M.\} and Natalia Korotkova",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

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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, A, Lambeau, G, Walker, MJ, Rush, JS, Korotkov, KV, Widmalm, G, van Sorge, NM & Korotkova, N 2019, 'Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides', Nature Chemical Biology, vol. 15, n.º 5, pp. 463-471. https://doi.org/10.1038/s41589-019-0251-4

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AU - Le Breton, Yoann

AU - El-Sayed, Najib M.

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AU - Morris, Andrew

AU - Lambeau, Gérard

AU - Walker, Mark J.

AU - Rush, Jeffrey S.

AU - Korotkov, Konstantin V.

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AU - van Sorge, Nina M.

AU - Korotkova, Natalia

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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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Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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