Phosphorylation of RpoD upregulates suilysin and enhances Streptococcus suis virulence.
- 1Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, No.2 Tiansheng Road, Beibei District, Chongqing, 400715, China.
- 2Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, No.2 Tiansheng Road, Beibei District, Chongqing, 400715, China. [email protected].
- 3Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, No.2 Tiansheng Road, Beibei District, Chongqing, 400715, China. [email protected].
Abstract
Streptococcus suis (S. suis) is a prevalent zoonotic pathogen that severely threatens the swine industry and human public health. Suilysin (SLY), a major pore-forming toxin of S. suis, is indispensable for bacterial hemolytic activity and systemic pathogenicity, yet the upstream regulatory mechanism controlling SLY production remains unclear. Serine/threonine kinase (STK) has been characterized to modulate bacterial physiology and virulence by phosphorylating multiple substrate proteins. Our previous phosphoproteomics analysis indicated that the housekeeping sigma factor RpoD was a potential STK substrate. In vitro phosphorylation assays combined with mass spectrometry, co-immunoprecipitation and site-directed mutagenesis confirmed that STK directly phosphorylated RpoD at Thr-208 residue. Phenotypic tests revealed that RpoD phosphorylation had no obvious impact on bacterial growth and biofilm formation but specifically promoted the thermotolerance and hemolytic activity of S. suis. Notably, the rpoD overexpression mutant strain SC19-rpoD significantly upregulated the transcription and protein production of SLY, whereas the phosphorylation-deficient mutant SC19-rpoD T208A abolished this promotion effect, indicating that Thr-208 phosphorylation is required for sly upregulation, although the underlying molecular mechanism remains to be fully defined. Furthermore, mouse infection models demonstrated that the SC19-rpoD T208A mutant exhibited alleviated splenic pathological injury, reduced bacterial loads in multiple organs, and significantly improved host survival, indicating that the loss of RpoD phosphorylation impairs S. suis virulence. Collectively, these findings demonstrate that STK-mediated phosphorylation of RpoD at Thr-208 is required for sly upregulation and contributes to the S. suis pathogenesis.
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BibTeX
@article{tian2026phosphorylation,
title = {{Phosphorylation of RpoD upregulates suilysin and enhances Streptococcus suis virulence.}},
author = {Yutong Tian and Zixuan Zhao and Hang Yin and Xinghong Liu and Jiaxiang Fu and Letao Gao and Yuqing Li and Rendong Fang and Lianci Peng},
journal = {Veterinary research},
year = {2026},
month = oct,
doi = {10.1186/s13567-026-01864-1},
url = {https://europepmc.org/article/MED/42963811},
note = {CC BY},
}
RIS
TY - JOUR
TI - Phosphorylation of RpoD upregulates suilysin and enhances Streptococcus suis virulence.
AU - Yutong Tian
AU - Zixuan Zhao
AU - Hang Yin
AU - Xinghong Liu
AU - Jiaxiang Fu
AU - Letao Gao
AU - Yuqing Li
AU - Rendong Fang
AU - Lianci Peng
PY - 2026
DA - 2026/10/30
JO - Veterinary research
DO - 10.1186/s13567-026-01864-1
UR - https://europepmc.org/article/MED/42963811
AB - Streptococcus suis (S. suis) is a prevalent zoonotic pathogen that severely threatens the swine industry and human public health. Suilysin (SLY), a major pore-forming toxin of S. suis, is indispensable for bacterial hemolytic activity and systemic pathogenicity, yet the upstream regulatory mechanism controlling SLY production remains unclear. Serine/threonine kinase (STK) has been characterized to modulate bacterial physiology and virulence by phosphorylating multiple substrate proteins. Our previous phosphoproteomics analysis indicated that the housekeeping sigma factor RpoD was a potential STK substrate. In vitro phosphorylation assays combined with mass spectrometry, co-immunoprecipitation and site-directed mutagenesis confirmed that STK directly phosphorylated RpoD at Thr-208 residue. Phenotypic tests revealed that RpoD phosphorylation had no obvious impact on bacterial growth and biofilm formation but specifically promoted the thermotolerance and hemolytic activity of S. suis. Notably, the rpoD overexpression mutant strain SC19-rpoD significantly upregulated the transcription and protein production of SLY, whereas the phosphorylation-deficient mutant SC19-rpoD T208A abolished this promotion effect, indicating that Thr-208 phosphorylation is required for sly upregulation, although the underlying molecular mechanism remains to be fully defined. Furthermore, mouse infection models demonstrated that the SC19-rpoD T208A mutant exhibited alleviated splenic pathological injury, reduced bacterial loads in multiple organs, and significantly improved host survival, indicating that the loss of RpoD phosphorylation impairs S. suis virulence. Collectively, these findings demonstrate that STK-mediated phosphorylation of RpoD at Thr-208 is required for sly upregulation and contributes to the S. suis pathogenesis.
SN - 0928-4249
SN - 1297-9716
ER -