Targeted Antibacterial Proteins May Offer Antibiotic Alternative

A novel antibacterial protein targeted against E. coli O157:H7 may offer a way to prevent or treat serious foodborne bacterial infections, as demonstrated in a study published in the December issue of Antimicrobial Agents and Chemotherapy.

Results in an animal model of E. coli infection showed that the orally administered protein, developed by AvidBiotics, Inc., could prevent or treat E. coli O157:H7-induced diarrhea and intestinal inflammation when administered either on a preventative basis or after the onset of diarrhea. Moreover, animals treated with the protein also carried and shed fewer of the E. coli O157:H7 bacteria in their feces.

"E. coli O157:H7 contamination of foods like ground meats or produce is a well-publicized public health problem, with life-threatening infection outbreaks reported around the world in recent years," says Dean Scholl, PhD, lead author of the publication. "Antibiotics are contraindicated for patients infected with enterohemorrhagic E. coli (EHEC) strains like O157:H7, because many of those drugs induce the bacteria to produce and release harmful toxins. Anti-diarrheal medications also do not benefit infected patients, as they cause the bacteria to be retained in the intestines, leading to greater toxin exposure. Thus the successful development of treatments that can prevent infection or limit symptoms and disease duration and the possible further spread of harmful bacteria without increasing toxin release could benefit both individual patients and affected communities."

The study published by Scholl and his collaborators at AvidBiotics and Brigham and Women's Hospital/Harvard Medical School assessed AvidBiotics' anti-E. coli O157 protein, termed an Avidocin protein, in a rabbit model of infection and reported that:

- The Avidocin protein remained active within the treated animals' intestinal tract for at least 24 hours post administration.
- When given shortly after the animals were infected with E. coli O157:H7 but before they developed active disease, the Avidocin protein inhibited bacterial colonization and/or the symptoms of infection. Animals that received the highest dose of protein studied did not develop diarrhea at any time during the experiment. In contrast, animals given buffer alone developed typical diarrhea within one to two days after infection, which worsened by the third day of the study.
- Analyses of colon tissue showed less severe intestinal inflammation in Avidocin protein-treated animals compared to controls. Avidocin protein administration also greatly reduced the number of E. coli O157:H7 recovered from the intestine and the stool of treated animals.

 
- When the anti-E. coli O157:H7 Avidocin protein was administered to infected animals already exhibiting disease symptoms, the existing diarrhea began to resolve in treated animals compared to animals treated with placebo. This reduction in diarrhea persisted until the experiment was terminated, 9 days post infection, at which time the feces of the treated animals appeared closer to feces from uninfected animals than the still largely liquid stool of the control animals. Thus, even after the onset of diarrhea in E. coli O157:H7-infected animals, administration of the anti-E. coli O157:H7 Avidocin protein could still mitigate the effects of infection.

 
"These findings suggest that an Avidocin protein targeted against E. coli O157:H7 offers promise for both the prevention and treatment of infection by this important enteric pathogen," says Scholl. "Moreover, this agent provides several significant advantages over conventional antibiotics, including a lack of drug-induced shiga toxin production and unintended collateral damage to normal intestinal bacterial populations. Additionally those rare variants of E. coli O157:H7 that emerge resistant to the anti-E. coli O157:H7 Avidocin protein are likely to have compromised virulence, or disease-causing properties."