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Peer-reviewedCC BYThe Microbe

Integrated transcriptomic and network analysis identifies novel regulatory hubs driving biofilm formation in

4 affiliations
  1. 1Department of Prosthodontics, School of Dentistry, Shahrekord University of Medical Sciences, Shahrekord, Iran; Corresponding author.
  2. 2Department of Orthodontics, School of Dentistry, Shahrekord University of Medical Sciences, Shahrekord, Iran
  3. 3Department of Mathematics, University of Shahrekord, Shahrekord, Iran
  4. 4Department of Prosthodontics, School of Dentistry, Shahrekord University of Medical Sciences, Shahrekord, Iran

Abstract

Streptococcus mutans is a key cariogenic bacterium that forms robust biofilms on tooth surfaces, playing a central role in dental caries. Biofilm development is mediated by multiple genes, including adhesion factors ( spaP ), glucan synthesis enzymes ( gtfB , gtfC ), glucan-binding proteins ( gbpC ), and regulatory pathways such as the quorum sensing comCDE system, the two-component vicRK system, and the alternative sigma factor sigX . In this study, we performed a comparative transcriptomic analysis of publicly available RNA-Seq datasets derived from dental plaque samples of caries-active and healthy individuals (n = 14, NCBI SRA) to identify key gene expression changes and regulatory networks associated with cariogenic biofilm formation. A total of 412 differentially expressed genes (DEGs) were identified, including 237 upregulated and 175 downregulated in caries-active samples. Notably, canonical biofilm-associated genes were highly upregulated: spaP (log2FC = +3.14), gtfB (log2FC = +2.87), gtfC (log2FC = +2.54), and gbpC (log2FC = +2.96). Quorum sensing regulators comC (log2FC = +1.45) and comE (log2FC = +0.98) were induced, while comD (log2FC = −0.87) was moderately downregulated. Functional enrichment analysis revealed significant involvement of pathways in quorum sensing, two-component signaling, carbohydrate metabolism, and oxidative stress response. Weighted Gene Co-expression Network Analysis (WGCNA) identified a module strongly correlated with the caries phenotype (r = 0.85), containing SMU_RS10050 as a potential novel regulatory hub. These results provide a systems-level understanding of S. mutans biofilm regulatory mechanisms in clinical datasets and highlight potential molecular targets for therapeutic intervention against cariogenic biofilms.

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BibTeX
@article{hasanvand2026integrated,
  title = {{Integrated transcriptomic and network analysis identifies novel regulatory hubs driving biofilm formation in}},
  author = {Mohsen Kazemi Hasanvand and Darab Gholami Boroujeni and Maryam Khosropour and Hosein Alavi Eshkaftaki and Matin Karbasion},
  journal = {The Microbe},
  year = {2026},
  month = oct,
  doi = {10.1016/j.microb.2026.100808},
  url = {https://doi.org/10.1016/j.microb.2026.100808},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Integrated transcriptomic and network analysis identifies novel regulatory hubs driving biofilm formation in
AU  - Mohsen Kazemi Hasanvand
AU  - Darab Gholami Boroujeni
AU  - Maryam Khosropour
AU  - Hosein Alavi Eshkaftaki
AU  - Matin Karbasion
PY  - 2026
DA  - 2026/10/30
JO  - The Microbe
DO  - 10.1016/j.microb.2026.100808
UR  - https://doi.org/10.1016/j.microb.2026.100808
AB  - Streptococcus mutans is a key cariogenic bacterium that forms robust biofilms on tooth surfaces, playing a central role in dental caries. Biofilm development is mediated by multiple genes, including adhesion factors ( spaP ), glucan synthesis enzymes ( gtfB , gtfC ), glucan-binding proteins ( gbpC ), and regulatory pathways such as the quorum sensing comCDE system, the two-component vicRK system, and the alternative sigma factor sigX . In this study, we performed a comparative transcriptomic analysis of publicly available RNA-Seq datasets derived from dental plaque samples of caries-active and healthy individuals (n = 14, NCBI SRA) to identify key gene expression changes and regulatory networks associated with cariogenic biofilm formation. A total of 412 differentially expressed genes (DEGs) were identified, including 237 upregulated and 175 downregulated in caries-active samples. Notably, canonical biofilm-associated genes were highly upregulated: spaP (log2FC = +3.14), gtfB (log2FC = +2.87), gtfC (log2FC = +2.54), and gbpC (log2FC = +2.96). Quorum sensing regulators comC (log2FC = +1.45) and comE (log2FC = +0.98) were induced, while comD (log2FC = −0.87) was moderately downregulated. Functional enrichment analysis revealed significant involvement of pathways in quorum sensing, two-component signaling, carbohydrate metabolism, and oxidative stress response. Weighted Gene Co-expression Network Analysis (WGCNA) identified a module strongly correlated with the caries phenotype (r = 0.85), containing SMU_RS10050 as a potential novel regulatory hub. These results provide a systems-level understanding of S. mutans biofilm regulatory mechanisms in clinical datasets and highlight potential molecular targets for therapeutic intervention against cariogenic biofilms.
SN  - 2950-1946
ER  -