Functional divergence of MdpS and MdpS2 reveals mucin-targeting strategies in Streptococcus oralis
(2025) In Journal of oral microbiology 17(1).- Abstract
Background: Mucin degradation is essential for understanding oral microbial adaptation, yet the enzymes involved remain incompletely understood. Herein, we have characterised two mucin-degrading proteases, MdpS and MdpS2, from the oral commensal Streptococcus oralis. Materials and methods: MdpS2 was characterised using physicochemical assays and substrate profiling and was compared to MdpS. Further Mdp characterisation included structural modelling, and functional assays analysing the gene expression during biofilm growth on salivary MUC5B, enzyme-induced biofilm dispersal, and mucus degradation analysed through nanoLC-MS/MS, sedimentation profiling, and microrheology. Results: MdpS2 shared conformational homology with MdpS despite low... (More)
Background: Mucin degradation is essential for understanding oral microbial adaptation, yet the enzymes involved remain incompletely understood. Herein, we have characterised two mucin-degrading proteases, MdpS and MdpS2, from the oral commensal Streptococcus oralis. Materials and methods: MdpS2 was characterised using physicochemical assays and substrate profiling and was compared to MdpS. Further Mdp characterisation included structural modelling, and functional assays analysing the gene expression during biofilm growth on salivary MUC5B, enzyme-induced biofilm dispersal, and mucus degradation analysed through nanoLC-MS/MS, sedimentation profiling, and microrheology. Results: MdpS2 shared conformational homology with MdpS despite low sequence identity and showed greater tolerance to pH and sodium chloride. Both genes were significantly upregulated during late stationary biofilm phase. MdpS and MdpS2 hydrolysed MUC5B extensively, with overlapping but distinct hydrolysis patterns. MdpS2 promoted biofilm dispersal and caused a pronounced reduction in MUC5B size and compactness. Microrheology showed selective modulation of MUC5B-rich mucus by MdpS2, while MdpS affected both MUC5B and MUC5AC networks. Conclusions: MdpS and MdpS2 exhibit complementary biochemical and functional profiles, supporting their roles in mucin degradation and biofilm remodelling. These findings advance our understanding of how early colonizing streptococci may interact with mucosal surfaces, influence biofilm dynamics and oral ecology, and suggest potential applications in targeting mucus-related disorders.
(Less)
- author
- Leo, Fredrik ; Nilsson, Jonas LU ; Arike, Liisa ; Kumar, Sahana ; Hilton, Emma ; Lood, Rolf LU ; Thornton, David J. ; Duncan, Gregg A. ; Svensäter, Gunnel and Wickström, Claes LU
- organization
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- biofilm dispersal, MdpS, MdpS2, microbial adaptation, MUC5B, mucin degradation, mucus rheology, oral microbiome, protease, Streptococcus oralis
- in
- Journal of oral microbiology
- volume
- 17
- issue
- 1
- article number
- 2571186
- publisher
- Taylor & Francis
- external identifiers
-
- pmid:41158440
- scopus:105019949022
- ISSN
- 2000-2297
- DOI
- 10.1080/20002297.2025.2571186
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
- id
- 67c3f4d4-3f0d-4458-9be4-67ca8ab41193
- date added to LUP
- 2026-01-15 12:50:28
- date last changed
- 2026-08-29 20:13:57
@article{67c3f4d4-3f0d-4458-9be4-67ca8ab41193,
abstract = {{<p>Background: Mucin degradation is essential for understanding oral microbial adaptation, yet the enzymes involved remain incompletely understood. Herein, we have characterised two mucin-degrading proteases, MdpS and MdpS2, from the oral commensal Streptococcus oralis. Materials and methods: MdpS2 was characterised using physicochemical assays and substrate profiling and was compared to MdpS. Further Mdp characterisation included structural modelling, and functional assays analysing the gene expression during biofilm growth on salivary MUC5B, enzyme-induced biofilm dispersal, and mucus degradation analysed through nanoLC-MS/MS, sedimentation profiling, and microrheology. Results: MdpS2 shared conformational homology with MdpS despite low sequence identity and showed greater tolerance to pH and sodium chloride. Both genes were significantly upregulated during late stationary biofilm phase. MdpS and MdpS2 hydrolysed MUC5B extensively, with overlapping but distinct hydrolysis patterns. MdpS2 promoted biofilm dispersal and caused a pronounced reduction in MUC5B size and compactness. Microrheology showed selective modulation of MUC5B-rich mucus by MdpS2, while MdpS affected both MUC5B and MUC5AC networks. Conclusions: MdpS and MdpS2 exhibit complementary biochemical and functional profiles, supporting their roles in mucin degradation and biofilm remodelling. These findings advance our understanding of how early colonizing streptococci may interact with mucosal surfaces, influence biofilm dynamics and oral ecology, and suggest potential applications in targeting mucus-related disorders.</p>}},
author = {{Leo, Fredrik and Nilsson, Jonas and Arike, Liisa and Kumar, Sahana and Hilton, Emma and Lood, Rolf and Thornton, David J. and Duncan, Gregg A. and Svensäter, Gunnel and Wickström, Claes}},
issn = {{2000-2297}},
keywords = {{biofilm dispersal; MdpS; MdpS2; microbial adaptation; MUC5B; mucin degradation; mucus rheology; oral microbiome; protease; Streptococcus oralis}},
language = {{eng}},
number = {{1}},
publisher = {{Taylor & Francis}},
series = {{Journal of oral microbiology}},
title = {{Functional divergence of MdpS and MdpS2 reveals mucin-targeting strategies in Streptococcus oralis}},
url = {{http://dx.doi.org/10.1080/20002297.2025.2571186}},
doi = {{10.1080/20002297.2025.2571186}},
volume = {{17}},
year = {{2025}},
}