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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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 languageEnglish
Pages (from-to)463-471
Number of pages9
JournalNature Chemical Biology
Issue number5
StatePublished - May 1 2019

Bibliographical note

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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