Alternatives to antibiotics: overview and engineered peptidoglycan hydrolases that reduce resistance development

Authors: Donovan, David; Khatibi, Piyum; LINE, ERIC - US Department Of Agriculture (USDA); Seal, Bruce; Bischoff, Kenneth

Submitted to: Proceedings of American Registry of Professional Animal Scientists
Publication Type: Abstract Only
Publication Acceptance Date: 4/24/2014
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over-used conventional antibiotics. A symposium in Paris, France, 2012 entitled “Alternatives to Antibiotics” was organized by Cyril Gay and the World Organization for Animal Health. This talk will briefly summarize the meeting findings and non-antibiotic approaches that can serve as novel antimicrobials, including: vaccines, probiotics, prebiotics, phytochemicals, essential oils, heavy metals, organic acids, bacteriophage, bacteriophage gene products, host-derived antimicrobials, small interfering RNAs, naturally occuring antibacterial lytic enzymes, recombinant and hyperimmune therapeutic antibodies, and immune enhancers. The remainder of the talk will describe the use of phage lytic enzymes to create antimicrobials that are refractory to resistance development. We have identified phage lytic enzymes with three unique enzyme activities that cut the cell wall structural element (peptidoglycan) of Staphylococcus aureus in three unique sites. Any one of the three enzymatic activities can kill the bacterium when exposed externally. When fused these three enzyme domains maintain each of their activities in the final triple-acting fusion protein. We have shown that these triple-acting enzyme constructs greatly reduce resistance development compared to the parental enzymes alone and are effective at reducing S. aureus nasal colonization by 97%. In an effort to reduce the need for antimicrobial growth promotants in animal feed, we have also worked with Bruce Seal, Athens, GA and Ken Bischoff, Peoria, IL to express Clostridium perfringens phage endolysins in yeast. Clostridium perfringens is a causative factor in necrotic enteritis that costs the poultry industry $2 billion annually. The goal of this work is to take advantage of the biofuel industry coproduct mash residue from yeast-driven ethanolic fermentations that is dried and sold as animal feed (dried distiller’s grains with soluble; DDGS). We have shown that yeast do express the C. perfringens phage lysin and the yeast-derived protein maintains anti-C. perfringens activity. Poultry feeding trials with the transgenic yeast are ongoing.