Novel Antibacterial Protein Blocks E. coli O157:H7 Infection

A paper described the use of a novel antibacterial protein to selectively destroy diarrhea-causing Escherichia coli O157:H7 both prior to and after infection in a rabbit model.

The biotech company AvidBiotics, Inc. (San Francisco, CA, USA) has been developing new antibacterial agents based on bioengineered pyocins. Pyocins are polypeptide toxins produced by some Pseudomonas aeruginosa strains that kill other types of bacteria by piercing their cell envelopes. AvidBiotics’ proprietary “Avidocin” pyocin efficiently kills antibiotic-resistant bacteria and does not promote the spread of multidrug resistance. Avidocin proteins are nontoxic to animals or nontargeted bacteria, and are biodegradable.

Results of studies in which Avidocin was used to treat rabbits exposed to E. coli O157:H7 were recently published in the December 2011 issue of the journal Antimicrobial Agents and Chemotherapy. In this paper, the investigators reported that Avidocin remained active within the treated animals' intestinal tract for at least 24 hours after administration.

When administered shortly after the animals were infected with E. coli O157:H7 but before they developed active disease, Avidocin inhibited bacterial colonization and prevented appearance of the symptoms of infection. Animals that received the highest dose of Avidocin did not develop diarrhea at any time during the experiment. In contrast, animals given only a buffer solution developed typical diarrhea within one to two days after infection, which worsened by the third day of the study. 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.

“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,” said contributing author Dr. Dean Scholl, a researcher at AvidBiotics, Inc. “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.”

“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,” said Dr. Scholl. “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.

Antidiarrheal 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.”

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