(81e) Engineering Probiotic Bacteria for Pathogen Reduction in Poultry Production

Foodborne illnesses are a costly public health concern affecting nearly 1 in 6 Americans each year. The effective treatment of these infections is being greatly compromised by the continuing emergence of antibiotic-resistant strains. Healthcare professionals are running out of viable treatment options for resistant infections which results in prolonged illnesses, increased mortality rates, and higher medical expenses. Estimates predict that, in the absence of a solution, drug-resistant infections will surpass cancer in total annual deaths by 2050.

With a major driving force for resistance development being the overuse of antibiotics, technologies are being sought to limit their injudicious use, particularly in food-producing animals. Over 50% of the antibiotics produced in the U.S. are consumed by livestock to promote animal growth and disease prevention. Often, this sub-therapeutic administration breeds bacterial resistance which can be transmitted to humans through food sources.

We have developed an antibiotic-alternative to decrease Salmonella carriage in poultry by engineering safe-to-consume probiotic bacteria with significant anti-Salmonella activity. Salmonella enteritidis (SE) is a leading bacterial agent of disease outbreaks and is primarily linked to poultry products. We modified the probiotic, E.coli Nissle 1917 (EcN), to produce high-titers of the antimicrobial peptide (AMP) , Microcin J25, which exhibits remarkable antagonistic activity against SE. AMPs have been researched for years for their antibiotic properties but have failed in translational success due to their high synthesis costs and rapid degradation rates in the body. Our novel use of a probiotic delivery vector has overcome these hurdles, enabling localized production among the hostâ??s natural microflora. By developing a strong synthetic-hybrid promoter system we were able to re-engineer the native microcin operon to enable controlled, robust, and well-characterized peptide production and secretion. Our in vivo studies have repeatedly demonstrated that a single treatment of our modified EcN is capable of dramatically reducing SE carriage in the GI tract of turkey poults, with better clearance than the traditional antibiotic, enrofloxacin. Treatment with the modified EcN has no adverse effects on bird growth. In performing an in-depth microbiome analysis, we have shown that there is no discernible impact on the health or diversity of the native microflora.

We will present the results of experiments that have involved over 600 turkey poults. We will discuss the strengths and limitations of synthetic biology techniques when used to develop a new antibiotic technology.