Shiga toxin-producing Escherichia coli (STEC) strains are important zoonotic foodborne pathogens, causing
diarrhea, hemorrhagic
colitis, and life-threatening
hemolytic uremic syndrome (HUS) in humans. However,
antibiotic treatment of STEC
infection is associated with an increased risk of HUS. Therefore, there is an urgent need for early and effective therapeutic strategies. Here, we isolated lytic T7-like STEC phage PHB19 and identified a novel O91-specific
polysaccharide depolymerase (Dep6) in the C terminus of the PHB19 tailspike
protein. Dep6 exhibited strong
hydrolase activity across wide ranges of pH (pH 4 to 8) and temperature (20 to 60°C) and degraded
polysaccharides on the surface of STEC strain HB10. In addition, both Dep6 and PHB19 degraded biofilms formed by STEC strain HB10. In a mouse STEC
infection model, delayed Dep6 treatment (3 h postinfection) resulted in only 33% survival, compared with 83% survival when mice were treated simultaneously with
infection. In comparison, pretreatment with Dep6 led to 100% survival compared with that of the control group. Surprisingly, a single PHB19 treatment resulted in 100% survival in all three treatment protocols. Moreover, a significant reduction in the levels of proinflammatory
cytokines was observed at 24 h postinfection in Dep6- or PHB19-treated mice. These results demonstrated that Dep6 or PHB19 might be used as a potential therapeutic agent to prevent STEC
infection.IMPORTANCE Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen worldwide. The Shiga-like toxin causes
diarrhea, hemorrhagic
colitis, and life-threatening
hemolytic uremic syndrome (HUS) in humans. Although
antibiotic therapy is still used for STEC
infections, this approach may increase the risk of HUS. Phages or phage-derived depolymerases have been used to treat
bacterial infections in animals and humans, as in the case of the "San Diego patient" treated with a phage cocktail. Here, we showed that phage PHB19 and its O91-specific
polysaccharide depolymerase Dep6 degraded STEC biofilms and stripped the
lipopolysaccharide (LPS) from STEC strain HB10, which was subsequently killed by serum
complement in vitro In a mouse model, PHB19 and Dep6 protected against STEC
infection and caused a significant reduction in the levels of proinflammatory
cytokines. This study reports the use of an O91-specific
polysaccharide depolymerase for the treatment of STEC
infection in mice.