Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide

Jeffrey S. Rush; Svetlana Zamakhaeva; Nicholas R. Murner; Pan Deng; Andrew J. Morris; Cameron W. Kenner; Ian Black; Christian Heiss; Parastoo Azadi; Konstantin V. Korotkov; Göran Widmalm; Natalia Korotkova

doi:10.1038/s41467-025-56205-1

Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide

Jeffrey S. Rush
, Svetlana Zamakhaeva
, Nicholas R. Murner
, Pan Deng
, Andrew J. Morris
, Cameron W. Kenner
, Ian Black
, Christian Heiss
, Parastoo Azadi
, Konstantin V. Korotkov
, Göran Widmalm
, Natalia Korotkova

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications. The predominant Glc modification, α-Glc, attached to position 2 of 3-rhamnose, is installed by SccN and SccM glycosyltransferases and is the site of the GroP addition. The minor Glc modifications are β-Glc linked to position 4 of 3-rhamnose installed by SccP and SccQ glycosyltransferases, and α-Glc attached to position 4 of 2-rhamnose installed by SccN working in tandem with an unknown enzyme. Both the major and the minor β-Glc modifications control bacterial morphology, but only the GroP and major Glc modifications are critical for biofilm formation.

Original language	English
Article number	954
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-56205-1
State	Published - Dec 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

The authors thank Dr. Catherine Chaton (University of Kentucky) for the help with figure preparation and Dr. Christopher D. Radka (University of Kentucky) for helpful discussion of ESI-MS analysis of phosphoglycolipids. This work was supported by NIH grants R01 DE028916 from the NIDCR and R01 AI143690 from the NIAID (to N.K.), and the Swedish Research Council (no. 2022-03014) and The Knut and Alice Wallenberg Foundation (to G.W.). Scanning electron microscopy was performed at the Electron Microscopy Center, which belongs to the National Science Foundation NNCI Kentucky Multiscale Manufacturing and Nano Integration Node, supported by ECCS−1542174. Carbohydrate composition/linkage analysis at the Complex Carbohydrate Research Center was supported by the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy grant DE-SC0015662 (to P.A.), as well as by NIH grant R24 GM137782 from the NIGMS (to P.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funders	Funder number
DOE Basic Energy Sciences
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences
Knut och Alice Wallenbergs Stiftelse
University of Kentucky
National Science Foundation NNCI Kentucky Multiscale Manufacturing
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...
Chemical Sciences, Geosciences, and Biosciences Division
Vetenskapsrådet	2022-03014
National Institute of Dental and Craniofacial Research	R01 AI143690
U.S. Department of Energy	DE-SC0015662, R24 GM137782
National Institutes of Health (NIH)	R01 DE028916
Division of Electrical, Communications and Cyber Systems	1542174

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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title = "Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide",

abstract = "Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications. The predominant Glc modification, α-Glc, attached to position 2 of 3-rhamnose, is installed by SccN and SccM glycosyltransferases and is the site of the GroP addition. The minor Glc modifications are β-Glc linked to position 4 of 3-rhamnose installed by SccP and SccQ glycosyltransferases, and α-Glc attached to position 4 of 2-rhamnose installed by SccN working in tandem with an unknown enzyme. Both the major and the minor β-Glc modifications control bacterial morphology, but only the GroP and major Glc modifications are critical for biofilm formation.",

author = "Rush, \{Jeffrey S.\} and Svetlana Zamakhaeva and Murner, \{Nicholas R.\} and Pan Deng and Morris, \{Andrew J.\} and Kenner, \{Cameron W.\} and Ian Black and Christian Heiss and Parastoo Azadi and Korotkov, \{Konstantin V.\} and G{\"o}ran Widmalm and Natalia Korotkova",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

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doi = "10.1038/s41467-025-56205-1",

language = "English",

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AU - Morris, Andrew J.

AU - Kenner, Cameron W.

AU - Black, Ian

AU - Heiss, Christian

AU - Azadi, Parastoo

AU - Korotkov, Konstantin V.

AU - Widmalm, Göran

AU - Korotkova, Natalia

PY - 2025/12

Y1 - 2025/12

N2 - Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications. The predominant Glc modification, α-Glc, attached to position 2 of 3-rhamnose, is installed by SccN and SccM glycosyltransferases and is the site of the GroP addition. The minor Glc modifications are β-Glc linked to position 4 of 3-rhamnose installed by SccP and SccQ glycosyltransferases, and α-Glc attached to position 4 of 2-rhamnose installed by SccN working in tandem with an unknown enzyme. Both the major and the minor β-Glc modifications control bacterial morphology, but only the GroP and major Glc modifications are critical for biofilm formation.

AB - Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications. The predominant Glc modification, α-Glc, attached to position 2 of 3-rhamnose, is installed by SccN and SccM glycosyltransferases and is the site of the GroP addition. The minor Glc modifications are β-Glc linked to position 4 of 3-rhamnose installed by SccP and SccQ glycosyltransferases, and α-Glc attached to position 4 of 2-rhamnose installed by SccN working in tandem with an unknown enzyme. Both the major and the minor β-Glc modifications control bacterial morphology, but only the GroP and major Glc modifications are critical for biofilm formation.

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Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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