This Small Business Technology Transfer (STTR) Phase I project will develop antimicrobial peptides (AMP) as an alternative to antibiotics that are used as growth promotants in animal feed. It is common practice to add low doses of medically important antibiotics to animal feed to improve production efficiency. However, this practice has been shown to lead to antibiotic-resistant bacterial strains, which have the potential to infect humans. As an alternative to traditional antibiotics, the goal is to test the potential of antimicrobial peptides. Because antimicrobial peptides are not used for human therapy, concerns regarding bacterial resistance are significantly diminished. The key limitation in using AMP has been the inability to produce them at cost effective levels. To overcome this challenge, the first step of this project will be to express a number of different AMP in filamentous fungal fermentations, which have the potential to produce tremendous amounts of recombinant protein at greatly reduced cost. If successful, this proof-of-concept study will justify additional research to determine the efficacy of AMP in livestock.
The broader impact/commercial potential of this project, if successful, is the reduction of antibiotic use in animal feeds. Some estimates place the worldwide market for animal-feed antibiotics at over $4 billion annually. However, to reduce bacterial antibiotic resistance, the FDA has recently published new guidance restricting traditional antibiotics to therapeutic use. Numerous alternatives to medically important antibiotics have been proposed, but the application of antimicrobial peptides shows great promise. The most significant limitation to their commercial application has been cost of production. Thus, the ability to economically manufacture these peptides would represent a significant benefit to the agricultural industry as it would allow farmers to maintain high levels of productivity while not generating antibiotic-resistant strains that pose a danger to humans.
Broader Impact: The technology developed in this research has potential to have significant impact on US national security. On September 18, 2014 President Barak Obama issued an Executive Order titled "COMBATING ANTIBIOTIC-RESISTANT BACTERIA." This document states "The rise of antibiotic-resistant bacteria…represents a serious threat to public health and the economy." It then suggests a number of strategies to address this threat. The document suggests "The Food and Drug Administration (FDA) in HHS, in coordination with the Department of Agriculture (USDA), shall continue taking steps to eliminate the use of medically important classes of antibiotics for growth promotion purposes in food-producing animals" (Section 5e). Further, that a Task Force will be established to facilitate and monitor implementation of the executive order and "…the Task Force shall describe steps that agencies can take to encourage the development of new and next-generation antibacterial drugs…for both the public and agricultural sectors..." This is precisely the goal of the research conducted for this award. Our goal was to generate proof-of-concept data providing evidence of a commercially viable product which could replace medically-relevant antibiotics in animal feed. Thus, when commercialized, this technology will have a significant impact on national security by reducing the development of antibiotic-resistant bacteria which negatively impact human health. Intellectual Merit: Research carried out under this award led to development of novel strategies to express recombinant peptides and proteins, with potent antibacterial activity, in filamentous fungi. Several strains were developed which express a peptide or protein with demonstrated antibacterial activity (Figure 1). To carry out assays, strains were grown in static culture and small amount of culture broth (10 microliters) was removed and spotted on a lawn of pathogenic bacteria. Cleared zones indicate antibacterial activity. To protect intellectual property, details (bacterial species, peptide and protein identity) are omitted. During this project, one invention disclosure was filed. This project also contributed to human capital, as one postdoctoral research associate was trained in a cross-disciplinary environment, combining his microbiology background with engineering experience in the context of developing a product for eventual commercialization.