Integrated Transcriptomic and Proteomic Analysis of the Pathogenic Mechanisms of Staphylococcus aureus-Induced...

Gangrenous mastitis is a severe form of mastitis in dairy goats that causes extensive tissue damage and has a poor prognosis, thereby substantially affecting the dairy goat industry; however, its molecular pathogenesis remains unclear. In this study, Staphylococcus aureus was used to establish a model of gangrenous mastitis in dairy goats. Mammary gland tissues were collected at 72 h post-inoculation for transcriptomic and proteomic sequencing, followed by integrated multi-omics analyses to systematically identify key regulatory pathways and candidate molecules associated with S. aureus-induced gangrenous mastitis. The results showed that clinical mastitis was characterized mainly by activation of pathways related to the acute inflammatory response, pathogen recognition, neutrophil chemotaxis, and phagocytic defense. In contrast, gangrenous mastitis involved broader molecular reprogramming, with significant enrichment of the TNF, IL-17, and NF-κB signaling pathways, complement and coagulation cascades, platelet activation, and extracellular matrix (ECM) remodeling. Protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), and validation of key molecules indicated that IL6, S100A8, THBS1, SERPINE1, and MMP9 may represent important nodes in disease progression. Collectively, these findings indicate that gangrenous mastitis is a complex infectious tissue-injury process driven by inflammatory amplification, aberrant immune-cell activation, complement-coagulation dysregulation, and tissue structural disruption. The identified molecules and pathways may facilitate the development of biomarker panels for early diagnosis and risk stratification and inform preventive and adjunctive therapeutic strategies targeting excessive inflammation, microcirculatory dysfunction, and ECM damage in dairy goats.