Rapid Generation of Targeted Antibacterial Agents in Response to Serious Food Safety Pathogens Detailed by AvidBiotics in PLoS ONE
Highly Specific Purocin™ Protein Quickly Generated Against German E. coli O104 Using Draft Genomic Sequence via AvidBiotics’ Antibacterial Protein Platform
South San Francisco, CA (March 14, 2012): A highly targeted bactericidal protein against the life-threatening foodborne E. coli O104 strain was rapidly created using AvidBiotics’ antibacterial Purocin™ protein technology, making use of rapidly acquired, published, draft genomic sequence data as detailed in a new publication in PLoS ONE. The strategy described offers a rapid-response platform with the potential to create targeted agents for use against emerging bacterial pathogens within days-to-weeks of acquiring the pathogen’s genome sequence.
“AvidBiotics has created a highly versatile technology platform for the generation of antibacterial proteins that specifically target and rapidly kill bacterial strains, offering important benefits in food security,” said AvidBiotics’ scientist, Dean Scholl, Ph.D., lead author on the new publication. “In collaboration with scientists from the U.S. Department of Agriculture, we’ve now shown that we can quickly generate such Purocin™ proteins against an emerging pathogen using only data acquired from its genome sequence, without necessarily having immediate access to the pathogen itself. This technology, in combination with the ever-increasing speed in which genome sequences can be generated and DNA synthesized, should provide a valuable tool for responding to newly emerging, re-emerging, and ever-changing bacterial threats.” The E. coli O104 strain, which initially emerged in Germany in spring 2011, was ultimately responsible for close to 4,000 illnesses and 48 deaths.
The AvidBiotics authors and their collaborators at the U.S. Department of Agriculture, Western Regional Research Center, describe how, using published genomic data from the German E. coli outbreak strain, they identified an O-antigen-specific prophage tail spike protein encoded in the pathogen’s genome. They synthesized the identified gene and fused it to the tail fiber gene of an R-type bacteriocin (a defense protein produced by certain bacteria against competing strains), and expressed the novel, engineered, antibacterial protein so that the tail fiber fusion was incorporated into an R-type bacteriocin structure. The resulting engineered protein demonstrated the ability to specifically bind and rapidly kill all tested E. coli strains that produce the O104 lipopolysaccharide antigen, including the German outbreak strain isolated from affected patients. None of many tested E. coli strains lacking the O104 antigen was sensitive to the O104-targeted protein, ensuring no unintended collateral damage.
About the AvidBiotics Antibacterial Protein Platform
AvidBiotics genetically engineers bactericidal proteins from R-type bacteriocins, proteins produced by some Pseudomonas aeruginosa strains for the purpose of killing competing bacteria. AvidBiotics’ antibacterial proteins specifically kill bacteria by binding to the bacterial cell and punching a hole in the cell envelope, causing membrane depolarization and rapid cell death.
AvidBiotics has previously demonstrated that Purocin™ proteins can be engineered to recognize and kill in a highly targeted and specific manner a variety of bacteria, including E. coli, Salmonella, and Shigella, thus serving as a platform for the production of numerous highly specific antibacterial agents. AvidBiotics is collaborating with food safety and hygiene leader, Ecolab Inc. (NYSE: ECL), to develop antibacterial proteins for use against E. coli O157:H7 in processing meat and other foods.
In addition to E. coli, a cause of both serious diarrheal disease and recurrent urinary tract infections, AvidBiotics is also currently developing Avidocin™ proteins against Pseudomonas aeruginosa, a common cause of severe pneumonia and wound infections, Clostridium difficile, the most common cause of hospital-acquired infections, and Acinetobacter, a bacterium associated with serious, often broadly antibiotic-resistant infections in Intensive Care Units and with injuries incurred by U.S. military deployed in Iraq and Afghanistan.
AvidBiotics is a developer of novel, non-antibody proteins as targeted therapeutics against bacteria, viral infections and cancers. The scaffolds of AvidBiotics’ proteins exhibit functional potency, e.g. killing, exceeding that of antibodies. AvidBiotics has two proprietary product platforms. The first is this new class of tailorable, targeted bactericidal agents for use in the treatment or prevention of specific bacterial infections. The second specifically flags virus-infected or cancerous cells for enhanced destruction by the Natural Killer and T-cells of the potent innate immunity system. AvidBiotics focuses on human therapeutic applications of its technologies, both on its own and in partnership with governmental agencies and research institutions, while taking advantage of further near-term collaborative opportunities offered by specific applications of its products and technology platforms in areas such as food safety, biodefense and animal husbandry.