Bacteriophage Potential for Reducing Agricultural Antibiotics

The current threats associated with antibiotics have caused more research and development resources to be devoted to the century old treatments of bacteriophages or “phages”, the natural enemies of bacteria. Current bioinformatic platforms are providing the previously unknown specifics of phage and bacteria interactions. Phages address many of the deficiencies of antibiotics: not universal, but bacteria specific; no withdrawal or residue problems of antibiotics; and multiple phages can be included in a “cocktail” for neutralizing multiple types or strains of bacteria.

Phage products have a presence within current food supply chains, including food processing aids, additives and environmental sanitation products which have been approved in the U.S. and countries of the European Union. Currently marketed products include protection against multiple strains of listeria, salmonella and E. coli as well as environmental sanitation products for seed treatments and food processing plants.

Numerous biocontrol products are approved for use with plants. Examples of current commercial phage products in the U.S. and Europe include: suppression of fire blight for apple and pear trees; reduction of bacterial spot for tomatoes and peppers; and prevention of soft rot disease for stored potatoes. These products typically are regionalized to address specific bacteria strains and updated with additional phages as necessary in spite of regulatory burden; e.g., European countries normally require re-registration of product for changes.

Current research and development activities also reflect a variety of phage related products for livestock and aquaculture production.

· The consequences of mastitis (inflammation of the udder) normally caused by various types of bacteria include direct and indirect costs of $ 25- $ 35 billion per year globally and have significant effects on dairy productivity. A private company is currently performing field trials with a phage cocktail for mastitis which is applied by syringe to the udder and has shown effectiveness against various bacterial pathogens, including Staph aureus bacteria which are often resistant to antibiotics. “In vivo” trials conducted by Milk South Africa also demonstrated a high level of phage effectiveness against Staph aureus.

· Enviphase, a European funded program conducted at AZTI research facilities of Spain developed a phage alternative for fish farm prophylactic antibiotics and is currently compiling the results of a yearlong test at a commercial aquaculture facility. The treatment can be impregnated within the feed or added to the water for fry and eggs. The preliminary cost analysis indicates the phage treatment costs will be less than the current antibiotic regime. Researchers have noted obstacles remain: no clear regulations regarding phage use; the absence of commercial phages of this type; and the small recognition factor within commercial aquaculture circles. Phages were also used by James Cook University to address hatchery mortality rates of 80–90% for redclaw crayfish. The phage treatment increased the survival rate to more than 80% during a complete hatchery season.

· The University of Leicester has successfully completed laboratory tests for the use of a 20 phage cocktail to combat 72 multi antibiotic resistant bacteria associated with hog production. The project is currently in field trials with the phage cocktail administered as a powder within feed. Another study composed of international researchers found a phage cocktail an effective antibacterial agent for suckling piglets and sows using multiple delivery agents.

· Comprehensive phage treatments soon may be widely available for poultry production; several potential products have completed development, but require viable partners for commercialization and continuing support. A recent study reviewed poultry related phage activities and concluded phages are potentially a sustainable alternative for bacterial control.

Modern biotechnology has provided the tools and methods to precisely apply the crude phages used for curing cholera in a Paris hospital during the early part of the 20th century. Further progress is dependent upon increased private and public funding and regulatory recognition of the unique characteristics of phages commensurate with the priority created by the international antibiotics crisis.

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