ORIGINAL RESEARCH article

Front. Vet. Sci.

Sec. Animal Nutrition and Metabolism

Volume 12 - 2025 | doi: 10.3389/fvets.2025.1644768

This article is part of the Research TopicAdvancements in Synthetic Microbiomes for Enhancing Animal HealthView all 12 articles

Mechanisms of Host-Bacterial Interactions During Escherichia coli or Staphylococcus aureus Infection of Mammary Epithelial Cells

Provisionally accepted
Zhengge  ZhaoZhengge Zhao1Zhiming  HouZhiming Hou2JIANMIN  CHAIJIANMIN CHAI1*Chunfang  LiChunfang Li3Tingyu  LiuTingyu Liu3Jianming  LiJianming Li3Shuyi  ZhangShuyi Zhang2Lei  ZhangLei Zhang2Yabin  MaYabin Ma3
  • 1Foshan University, Foshan, China
  • 2Shenyang Agricultural University, Shenyang, China
  • 33Hebei Animal Husbandry and Breeding Work Station, Shijiazhuang, China

The final, formatted version of the article will be published soon.

Mastitis is one of the costliest diseases in the dairy industry. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are the two most predominant pathogens. However, the specific molecular mechanisms underlying the interactions between these pathogens and bovine mammary epithelial cells, especially for two pathogenic co-infections, remain poorly understood. Here, this study employed high-throughput RNA sequencing to comprehensively analyze the gene expression changes in bovine mammary epithelial cells upon individual and co-infection with E. coli and S. aureus. Transcriptomic analysis identified 282 differentially expressed genes (DEGs) in the E. coliinfected group (E group), with 246 upregulated and 36 downregulated genes. Notably, proinflammatory genes (CXCL8, GRO1, CCL20) were significantly induced, and functional enrichment analysis demonstrated robust activation of inflammatory pathways including TLR/NF-κB and IL-17 signaling cascades. In contrast, the S. aureus-infected group (S group) exhibited 354 DEGs (314 upregulated, 40 downregulated), featuring pathogen-specific upregulated genes (ESM1, IL18RAP). Functional annotation revealed predominant involvement of metabolic processes, particularly ATP metabolism and chaperone complex activities. The co-infection group (ES group) displayed 307 DEGs (277 upregulated, 30 downregulated), demonstrating a unique "inflammatory-metabolic" dualmode signature that integrated inflammatory features from the E group with metabolic reprogramming characteristics of the S group. Protein-protein interaction network analysis further delineated pathogen-specific hubs: inflammatory mediators (CXCL8, CCL20, IL6) in the E group, molecular chaperones (CCT5, RUVBL1/2) in the S group, and a distinctive IL6-FBL-centered network in co-infection. These findings elucidate pathogen-specific molecular mechanisms at the transcriptomic level, particularly revealing a unique "inflammatory-metabolic" dual-mode regulatory network during co-infection states. These findings provide new insights into the pathogenesis of mastitis and provide a theoretical basis for developing targeted prevention and control strategies.

Keywords: RNA-Seq, bovine, MAC-T cells, Escherichia coli, Staphylococcus aureus, Transcriptomics, PPI, Mammary epithelial cells

Received: 10 Jun 2025; Accepted: 09 Jul 2025.

Copyright: © 2025 Zhao, Hou, CHAI, Li, Liu, Li, Zhang, Zhang and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: JIANMIN CHAI, Foshan University, Foshan, China

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