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

Producción científica: Article › revisión exhaustiva

Resumen

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.

Idioma original	English
Número de artículo	954
Páginas (desde-hasta)	954
Número de páginas	16
Publicación	Nature Communications
Volumen	16
N.º	1
DOI	https://doi.org/10.1038/s41467-025-56205-1
Estado	Published - ene 22 2025

Nota bibliográfica

Financiación

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.

Financiadores	Número del financiador
U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID)	R24 GM137782
NIH	R01 AI143690
NIDCR
NIAID	2022-03014
Swedish Research Council	ECCS-1542174
Knut and Alice Wallenberg Foundation	DE-SC0015662
Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy
NIGMS

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10.1038/s41467-025-56205-1

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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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AU - Morris, Andrew J

AU - Kenner, Cameron W

AU - Black, Ian

AU - Heiss, Christian

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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

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