Oral bacteriophage therapy effectively prevent and control of Clostridium perfringens type c infections in newborn piglets

Clostridium perfringens (C. perfringens) type C exhibits strong pathogenicity, often leading to swine dysentery, severely affecting the economic efficiency of the pig farming industry. Bacteriophages as bacterial viruses have many natural advantages and are potent candidates for controlling bacterial infections. In this study, a lytic C. perfringens phage designed as vB_CpeP_15N3 was isolated with the host C. perfringens type C CVCC1155, and its potential for therapy was determined in vitro and in vivo. Despite the narrow host range, phage vB_CpeP_15N3 exhibited a large burst size of 102 PFU/cell following a short latent period of 10 min. In addition, phage vB_CpeP_15N3 remained stable at temperatures ranging from 4 to 50°C and pH levels from 5 to 9 and had a strong antibacterial effect in vitro. Through whole-genome analysis, phage vB_CpeP_15N3 belongs to the family Guelinviridae, genus Brucesealvirus with no genes related to lysogeny and bacterial virulence or resistance. We further demonstrated that phage vB_CpeP_15N3 by oral administration for preventive purposes could significantly alleviate clinical symptoms and jejunal lesions of newborn piglets through the reduced colonization of C. perfringens type C in the jejunum and the level of CPB toxin in the content of jejunum in the newborn piglet model of CVCC1155 infection. In addition, phage vB_CpeP_15N3 by oral administration for preventive purposes could improve the diversity and abundance of the jejunum microbiota in newborn piglets. Moreover, the prevention by phage vB_CpeP_15N3 obtained more effective therapeutic results than phage and gentamicin treatments. Taken together, these findings suggested that phage vB_CpeP_15N3 is a promising alternative of antibiotics for preventing and controlling C. perfringens type C infection of newborn piglets.