Efficacy of lytic bacteriophages isolated from sewage-treatment plants in Mbarara district, Uganda against ciprofloxacin-resistant Salmonella Typhi in a mice infection model

Abstract

BACKGROUND: Resistance to antibiotics often leads to therapeutic failure and mortality, especially in resource-limited countries including Uganda. This necessitates the search for efficacious and safe alternatives. The study determined the in vivo efficacy of isolated lytic bacteriophages from sewage treatment plants, against ciprofloxacin-resistant Salmonella Typhi in Mbarara district, Uganda. METHODS: A laboratory based experimental study was conducted. Twelve samples obtained from two sewage treatment plants within Mbarara district, Southwestern Uganda; Kakoba and Taso were used for isolation of bacteriophages using the double agar overlay plaque assay. The isolated phages were assayed for both biological and physico-chemical characteristics. A mice infection model that included; bacteria + phage, bacteria + SM buffer, bacteria + ciprofloxacin antibiotic groups and phage only were used to assess the in vivo efficacy of bacteriophage cocktail against ciprofloxacin resistant Salmonella Typhi after intraperitoneal administration. The bacterial loads and phage titres from the lungs, intestines, liver, and kidney were determined using surface spreading and double agar overlay plaque assay. Data was analyzed using SPSS-26 to compute descriptive statistics and statistical significance was considered at P ≤ 0.05. RESULTS: The selected phages exhibited lytic activity against ciprofloxacin-resistant S. Typhi, with an average host range limited to S. Typhi species. The phage cocktail rapidly decreased S. Typhi counts in blood, liver, spleen intestines, and kidney to 0 CFU/mL within 48 h compared to ciprofloxacin-treated mice. The phages were completely cleared rapidly in the spleen, kidney, and blood within 60, 96, and 120 h, respectively. Treatment with a phage cocktail caused significant reductions in the weights of the liver and intestines compared to ciprofloxacin-treated mice. CONCLUSIONS: The results highlight the lytic properties of bacteriophages against ciprofloxacin-resistant S. Typhi, suggesting its use in antibacterial therapy. RECOMMENDATIONS: The study recommends molecular characterization, pharmacokinetic, histological effects, and immunological responses to establish the safety of phage cocktails for therapeutic use in humans. CLINICAL TRIAL NUMBER: Not applicable.