Therapeutic Efficacy of Phage PIZ SAE-01E2 Against Abortion Caused by Salmonella abortus equi in Mice.

Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is a frequently reported pathogen causing abortion in mares. In this study, the preventive and therapeutic effects of phage PIZ SAE-01E2 against S. abortus equi in a mouse model of abortion was investigated. Phage PIZ SAE-01E2 was stable at different temperatures (4 ∼ 70 °C) and pH values (4 ∼ 10) and could lyse the majority of the tested Salmonella strains (25/28) of serotype O:4 and O:9. There is no lysogenic, toxin or antibiotic-resistant related gene in the genome of PIZ SAE-01E2. All of these characteristics indicated PIZ SAE-01E2 has potential for phage therapy. In in vivo experiments, 2 × 103 CFU/mouse of S. abortus equi ATCC 9842 was sufficient to lead to murine abortion (gestational day 14.5) within 48 h. A single dose of intraperitoneal inoculation of PIZ SAE-01E2 (108 PFU/mouse, MOI = 105) 1 h before or after S. abortus equi challenge provided effective protection to all pregnant mice (10/10). The bacterial loads in the placenta and uterus of the infected mice were both significantly decreased ( 106 CFU/g). In addition, the levels of inflammatory cytokines in the placenta and blood of the mice in the phage administration groups were significantly reduced (P < 0.05) compared to that of the control group. Altogether, this indicated that PIZ SAE-01E2 showed potential to block abortions induced by S. abortus equiin vivoImportanceS. abortus equi is an important pathogen that can induce abortions in mares. Although S. abortus equi has been well controlled in Europe and United States due to strict breeding and health policies, it is still widespread in African and Asian countries and has proven difficult to control. In China, the abortions in donkeys caused by S. abortus equi have also been reported. So far, there is no commercial vaccine. Thus, exploiting alternative efficient and safety strategies to control S. abortus equi infection is essential. In this study, a new lytic phage PIZ SAE-01E2 infecting S. abortus equi was isolated and characteristics of PIZ SAE-01E2 indicated it has potential for phage therapy. A single dose of intraperitoneal inoculation of PIZ SAE-01E2 before or after S. abortus equi challenge provided effective protection to all pregnant mice. Thus, PIZ SAE-01E2 showed potential to block abortions induced by S. abortus equiin vivo.