Study Published in mBio Shows that Avidocin™ Proteins Prevent Clostridium Difficile Infection in Mice without Harming Protective Gut Bacteria
Data Demonstrate Potency and Selectivity of Targetable, Highly Precise Antibacterials with Applications in Bacterial Disease and Microbiome Research
South San Francisco, Calif., March 24, 2015 – A study published today in mBio, an open-access journal of the American Society for Microbiology, demonstrated that Avidocin™ proteins administered to mice prevented infection by Clostridium difficile bacteria without disrupting the healthy gut bacteria. The study was led by researchers from AvidBiotics, the developers of the Avidocin technology, in collaboration with scientists at the Sanger Institute and the Cleveland VA Medical Center.
Avidocin™ proteins were able to selectively remove the disease-causing bacteria from the gut in the study, demonstrating the potential to be the first prophylactic treatment for C. difficile infection that does not disrupt the microbiome. By leaving healthy gut bacteria intact, the therapies preserve natural resistance to colonization by disease-causing microbes and simultaneously reduce the need for broad spectrum antibiotics.
“C. difficile is an urgent public health threat, with Centers for Disease Control and Prevention reporting that rates continue to rise to alarming levels of nearly 500,000 people infected and 40,000 people killed annually in the US, ,” said David Martin, M.D., chief executive officer of AvidBiotics. “These pathogenic bacteria are able to propagate, produce toxins and cause disease in people that have had their healthy intestinal bacteria disturbed by a broad-spectrum antibiotic. The AvidBiotics’ team has shown that Avidocins can, with exquisite precision, prevent C. difficile from colonizing the microbiota while leaving the body’s natural protection against infections unharmed. Avidocins are expected to be ready for clinical trials in 2016.”
In the study, Avidocins were used to prevent colonization in an animal model designed to mimic a typical exposure to C. difficile spores encountered by patients in healthcare facilities. The Avidocin studied was constructed using genes from an “epidemic strain” of C. difficile (NAP1/BI/027) and killed all tested bacteria from this predominant North American strain. At the effective dose, Avidocins did not alter the bacterial composition of the healthy gut or compromise its natural, effective and long-lasting resistance to colonization by disease-causing bacteria.
Avidocins are genetically modified versions of R-type bacteriocins – proteins naturally produced by bacteria to kill competing strains. These molecules are extraordinarily potent, with a single bacteriocin being sufficient to kill a bacterium. Avidocins are tailored to target particular species or strains of bacteria, often with the targeting protein encoded within the DNA of the target bacterium itself. The technology leverages the abundance of new microbial genomic information being generated to rapidly construct novel antibacterials and can be rapidly re-engineered to kill emerging dangerous bacterial strains.
Avidocin technology also enables a new approach to microbiome research through selective elimination of a single species or strain of bacteria. Avidocins could be the first technology of its kind to enable this selective elimination, allowing researchers to better understand the role an individual strain plays in human health and disease. The application of Avidocin proteins to manipulate the gut bacterial population could expand into therapeutic applications for broader disease areas, such as allergy, autoimmunity, diabetes, and obesity.
AvidBiotics is also applying its precision antibacterial approach for non-human uses. The food and animal health industries are undergoing strong pressure to eliminate antibiotics and chemicals from their products and processes. With this in mind, AvidBiotics is currently developing Purocin™ proteins targeting E. coli, Salmonella and Listeria for food safety applications with its partner, E.I. DuPont de Nemours & Co. Due to their specificity and apparent safety, Purocin proteins offer a promising new technology for safely protecting the food supply from dangerous bacterial contaminants.
AvidBiotics has developed a portfolio of therapeutic proteins designed to selectively destroy target cells with surgical precision, including pathogenic bacteria, viruses and cancer cells. Its new class of narrow-spectrum bacteria-killing agents, known as Avidocin proteins, is a potential solution to overcome two key problems with broad-spectrum antibiotics: the rampant spread of drug resistance and the unintended damage to healthy, protective bacteria that comprise the microbiota. In addition, AvidBiotics has created a Micacide™ protein platform for the creation of therapeutics that activate the immune system to destroy cancer cells and cells infected by viruses. For more information on AvidBiotics, please visit the company’s web site.