数字农科院2.0

Streptococcus agalactiae suppresses milk protein synthesis in bovine mammary epithelial cells via PGK1-mediated inhibition of the JAK2/STAT5 signalling pathway

文献类型： 外文期刊

作者： Yankun Zhao;Yating Wu;Xianlan Ma;Huimin Liu;Lu Meng;He Chen;Jiaqi Wang;Nan Zheng;Cheng Wang

作者机构：

关键词： Apoptosis;Bovine mastitis;JAK2/STAT5 pathway;Mammary epithelial cells;PGK1;Streptococcus agalactiae

期刊名称： International Journal of Dairy Technology

ISSN： 1364-727X

年卷期： 2025 年 78 卷 4 期

页码：

收录情况： SCIE（2025版）

摘要： Background: Streptococcus agalactiae is a major pathogen of bovine mastitis. Phosphoglycerate kinase 1 (PGK1) is considered a multifunctional virulence factor in bacterial pathogens and plays a novel role in host–pathogen interaction: PGK1 facilitates energy acquisition and immune evasion in intracellular group B streptococcus infection; PGK1 enhances systemic dissemination by facilitating evasion of host immunity in S. pyogenes infection; PGK1-derived S. pneumoniae promotes epithelial adhesion and lung colonisation. Understanding the mechanisms underlying mammary epithelial cell damage and milk synthesis inhibition is critical for developing mastitis prevention strategies. Aim: To establish an intracellular infection model of S. agalactiae in bovine mammary epithelial cells (BMECs) to investigate the effects on apoptosis and elucidate mechanisms disrupting milk synthesis with a focus on PGK1 and the JAK2/STAT5 pathway. Methods: BMECs were infected with S. agalactiae (multiplicity of infections: 20–100, 2–8 h). Cytotoxicity, apoptosis and cytoskeletal changes were assessed. PGK1 expression, apoptosis markers and milk synthesis mediators (JAK2/STAT5/ELF5/CSN2) were analysed via qRT-PCR and western blot. PGK1 knockdown and JAK2 inhibitor (50 μM AG490 for 24 h [DMSO vehicle control]) treatment validated the pathway involved. Major Findings: S. agalactiae infection caused time- and dose-dependent cytotoxicity (maximal LDH release: ~40% increase, P < 0.05; cell viability reduction: ~35%, P < 0.05 at an MOI = 100 for 8 h). Infection induced cytoskeleton rearrangement and apoptosis (apoptosis rate, 25.3% vs. control, 5.1%, P < 0.05) and upregulated PGK1 expression. PGK1 knockdown reduced apoptosis by ~50% (P < 0.05). S. agalactiae downregulated JAK2/STAT5/ELF5 (P < 0.05) and impaired milk protein synthesis. CSN2 expression was decreased by ~60% (P < 0.05) and partially rescued by PGK1 knockdown but exacerbated by AG490. Implications: PGK1-mediated apoptosis and JAK2/STAT5/ELF5 suppression are key mechanisms in S. agalactiae inhibiting milk synthesis. Molecular targets for mitigating mastitis-induced milk loss were identified, supporting dairy safety and productivity strategies.

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