PoGPx-7, a glutathione peroxidase homolog from teleosts, exhibits bactericidal activity and activates host immune cells against bacterial infection.

In mammals, glutathione peroxidase 7 (GPx-7) is a member of the GPx family that exhibits peroxidase activity. Its immunological functions, especially in host defense against bacterial infection, remain unexplored in lower vertebrates. In this study, we identified a GPx-7 homolog from Paralichthys olivaceus (PoGPx-7) and investigated its roles during Vibrio alginolyticus infection. PoGPx-7 possesses a conserved GSH-Px domain and carries positive net charges. PoGPx-7 was constitutively expressed in various tissues, with significant upregulation upon bacterial challenge. Recombinant PoGPx-7 (rPoGPx-7) exhibited GPx activity and bound to V. alginolyticus via interaction with lipopolysaccharide and peptidoglycan. In addition, rPoGPx-7 could directly kill bacteria by disrupting membrane integrity, leading to severe structural damage and content leakage. The bactericidal activity was modulated by protein concentration, pH, temperature, and Zn2+. Furthermore, rPoGPx-7 bound to peripheral blood leukocytes (PBLs), reduced bacterial attachment and LDH release, and protected PBLs from cell death. It also significantly enhanced phagocytosis, respiratory burst, and acid phosphatase activity of PBLs. In vivo administration showed that rPoGPx-7 reduced bacterial loads in the tissues, and improved fish survival, whereas knockdown of PoGPx-7 increased susceptibility to infection. These findings provide the first evidence that teleosts GPx-7 functions as a dual-effector molecule with direct bactericidal activity and immunomodulatory capacity, providing an immunological insight of GPx family members on resistance bacterial infection.