A critical role for host-derived cystathionine-β-synthase in Staphylococcus aureus-induced udder infection

Cystathionine-β-synthase (CBS) catalyzes the first step of the transsulfuration pathway. The role of host-derived CBS in Staphylococcus aureus (S. aureus)-induced udder infection remains elusive. Herein, we report that S. aureus infection enhances the expression of CBS in mammary epithelial cells in vitro and in vivo. A negative correlation is present between the expression of CBS and inflammation after employing a pharmacological inhibitor/agonist of CBS. In addition, CBS achieves a fine balance between eliciting sufficient protective innate immunity and preventing excessive damage to cells and tissues preserving the integrity of the blood-milk barrier (BMB). CBS/H₂S reduces bacterial load by promoting the generation of antibacterial substances (ROS, RNS) and inhibiting apoptosis, as opposed to relying solely on intense inflammatory reactions. Conversely, H₂S donor alleviate inflammation via S-sulfhydrating HuR. Finally, CBS/H₂S promotes the expression of Abcb1b, which in turn strengthens the integrity of the BMB. The study described herein demonstrates the importance of CBS in regulating the mammary immune response to S. aureus. Increased CBS in udder tissue modulates excessive inflammation, which suggests a novel target for drug development in the battle against S. aureus and other infections.