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...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56205-1
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author 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
author_facet 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
author_sort Jeffrey S. Rush
collection DOAJ
description 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.
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spelling doaj-art-eb86e35ea54f4cfbac160017ea64d6d32025-01-26T12:41:56ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56205-1Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharideJeffrey S. Rush0Svetlana Zamakhaeva1Nicholas R. Murner2Pan Deng3Andrew J. Morris4Cameron W. Kenner5Ian Black6Christian Heiss7Parastoo Azadi8Konstantin V. Korotkov9Göran Widmalm10Natalia Korotkova11Department of Molecular and Cellular Biochemistry, University of KentuckyDepartment of Microbiology, Immunology and Molecular Genetics, University of KentuckyDepartment of Microbiology, Immunology and Molecular Genetics, University of KentuckyDepartment of Pharmaceutical Sciences, College of Pharmacy, University of KentuckyDivision of Cardiovascular Medicine and the Gill Heart Institute, University of KentuckyDepartment of Microbiology, Immunology and Molecular Genetics, University of KentuckyComplex Carbohydrate Research Center, University of GeorgiaComplex Carbohydrate Research Center, University of GeorgiaComplex Carbohydrate Research Center, University of GeorgiaDepartment of Molecular and Cellular Biochemistry, University of KentuckyDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm UniversityDepartment of Molecular and Cellular Biochemistry, University of KentuckyAbstract 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.https://doi.org/10.1038/s41467-025-56205-1
spellingShingle 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
Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide
Nature Communications
title Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide
title_full Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide
title_fullStr Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide
title_full_unstemmed Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide
title_short Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide
title_sort structure and mechanism of biosynthesis of streptococcus mutans cell wall polysaccharide
url https://doi.org/10.1038/s41467-025-56205-1
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