Phage Cocktail Targeting STEC O157:H7 Has Comparable Efficacy and Superior Recovery Compared with Enrofloxacin in an Enteric Murine Model

Abstract

ABSTRACT O157:H7 is the most important Shiga toxin-producing Escherichia coli (STEC) serotype in relation to public health. Given that antibiotics may contribute to the exacerbation of STEC-related disease and an increased frequency of antibiotic-resistant strains, bacteriophage (phage) therapy is considered a promising alternative. However, phage therapy targeting enteric pathogens is still underdeveloped with many confounding effects from the microbiota. Here we comprehensively compared the therapeutic efficacy of a phage cocktail with the antibiotic enrofloxacin in a mouse model of STEC O157:H7 EDL933 infection. Enrofloxacin treatment provided 100% survival and the phage cocktail treatment provided 90% survival. However, in terms of mouse recovery, the phage cocktail outperformed enrofloxacin in all measured outcomes. Compared with enrofloxacin treatment, phage treatment led to a faster elimination of enteric pathogens, decreased expression levels of inflammatory markers, increased weight gain, maintenance of a stable relative organ weight, and improved homeostasis of the gut microbiota. These results provide support for the potential of phage therapy to combat enteric pathogens and suggest that phage treatment leads to enhanced recovery of infected mice compared with antibiotics. IMPORTANCE With the increasing severity of antibiotic resistance and other adverse consequences, animal experiments and clinical trials investigating the use of phages for the control and prevention of enteric bacterial infections are growing. However, the effects of phages and antibiotics on organisms when treating intestinal infections have not been precisely studied. Here, we comprehensively compared the therapeutic efficacy of a phage cocktail to the antibiotic enrofloxacin in a mouse model of STEC O157:H7 EDL933 infection. We found that, despite a slightly lower protection rate, phage treatment contributed to a faster recovery of infected mice compared with enrofloxacin. These results highlight the potential benefits of phage therapy to combat enteric infections.

Keywords

• phage cocktail
• antibiotics
• gut microbiota
• therapy