Klebsiella pneumoniae causes mammary gland damage via FNIP1-mediated mitochondrial dysfunction.

Klebsiella pneumoniae (K. pneumoniae) is one of the pathogens causing clinical mastitis of bovine. Previous studies have demonstrated that mitochondrial damage and dysfunction are important mechanisms of mastitis in dairy cattle. Folliculin interacting protein 1 (FNIP1) is a major metabolic regulator of mitochondrial function with proinflammatory capabilities, but its role in K. pneumoniae-induced mastitis is yet to be elucidated. Thus, the studies were conducted to clarify the role of FNIP1-mediated mitochondrial function in mastitis caused by K. pneumoniae in vivo and in vitro. The experiments verified that K. pneumoniae caused decrease of milk fat and protein synthesis evidently in the mammary glands and bovine mammary epithelial cells (BMECs), accompanied by an imbalance in mitochondrial fission and fusion, increased mitochondrial permeability transition pore opening, decreased membrane potential and ATP content. While the enhancement of mitochondrial function alleviated K. pneumoniae-induced BMECs injury via relieving milk fat and protein dyssynthesis. Notably, transcriptomic analysis revealed that FNIP1 expression was upregulated in BMECs induced by K. pneumoniae. Further investigations revealed FNIP1 silencing improved milk synthesis by alleviating mitochondrial dysfunction caused by K. pneumoniae infection, and further inhibiting the activation of inflammatory factors, which in turn prompted the mammary recovery. In conclusion, K. pneumoniae inhibited mitochondrial function by activating FNIP1, which reducing the synthesis of milk fat and protein, thereby in turn lowers milk quality and induced mastitis. This study showed that FNIP1 has the potential as a novel target for the prevention and control of bovine mastitis.