Pre-treatment with phages achieved greater protection of mice against infection with Shiga toxin-producing Escherichia coli than post-treatment

Abstract

Shiga toxin-producing Escherichia coli (STEC) is a group of pathogen that can cause various diseases in both humans and animals, such as watery diarrhea, hemorrhagic colitis, and uremia syndrome. Due to the serious situation of antibiotic resistance, phage therapy is considered to have a great potential in combating bacterial diseases. In this study, three phages (NJ-10, NJ-20, and NJ-38) with strong abilities to lyse virulent STEC strain CVCC193 cells in vitro were isolated. Subsequently, the therapeutic effects of the three phages were investigated in mice infected with CVCC193 cells. The results showed that the survival rates of mice injected with the phages at 3 h after challenge with CVCC193 cells were 40%–50%, while the survival rates of mice injected with the phages at 24 h before challenge were 80%–100%, indicating that pre-treatment with phages had better therapeutic effects than post-treatment. Pathological changes, bacterial loads in different organs, and serum levels of inflammatory factors of the infected mice were also detected. The results showed that the mice injected with the phages at 3 h after or 24 h before challenge with CVCC193 cells had significantly decreased organ lesions, bacterial loads, and serum levels of inflammatory factors as compared to infected mice without phage treatment. These results suggested that phages NJ-10, NJ-20, and NJ-38 can potentially protect against STEC infections.