SR9094 - Novel Saccharide Modifiers of Bacterial Colonization

Research:

Dr. M. Anthony Hayes, Dept. of Pathobiology, University of Guelph

Objectives:

1. To define protein-lectin mechanisms of resistance and susceptibility to endemic bacterial infections (Actionbacillus, E. coli, Salmonella, Streptococcus ss) of livestock (swine, poultry, cattle).
   

2. To develop functional binding assays in which effective competitors can be identified.
   

3. To evaluate naturally occurring milk and egg-yolk oligosaccharides that compete, to define the chemical properties of effective competitors of lectin-mediated bacterial adhesion.
   

4. To define natural product-derived feed additivies that could be used as competitors that reduce bacterial colonization, carrier status and reduce production losses associated with bacterial infections.

Expected Benefits:

The potential development of value-added antimicrobial competitors for animal rations will be an economic benefit to the Ontario livestock feed production and processing industries, and to the pork, poultry and egg production and marketing industries. The specification and maintenance of disease resistant animal phenotypes is also potentially valuable to primary breeding stock producers in Ontario.

Summary of Research Results:

Two approaches were attempted:

1. To develop novel oligoaminosaccharides that might competitively block colonization when incorporated into animal feed. We made forms of soluble chitin modified from marine crustaceans and showed that these have the required ability to compete lectin binding to the pig pathogenic bacterium Actinobacillus pleuro-pneumoniae. However, concentrations required for competitive dissociation were relatively high, and this compromised the prospects for preparation of suitable low cost chitins. The commercial feasibility of this approach deteriorated as two successive industrial suppliers with technology to supply the base chitin discontinued production of their lower value products.
   
   
2. To develop new genetic options for control of bacterial diseases in livestock. We discovered and sequenced a new pig lectin named mannan-binding lectin-A (MBL-A) that binds many pig bacterial pathogens. We developed a method for screening pigs for genetic mutations in this MBL gene and we identified several single nucleotide polymorphisms (SNPs) distributed among various breeds and lines of Ontario swine. One SNP is a genetic mutation similar to several human MBL SNPs that increase susceptibility of young children to various infections. We have also discovered a common genetic defect that prevents many pigs from producing the other form (MBL-C). This appears to resemble genetic defects in humans that greatly reduce blood concentrations of human MBL, and thereby increase susceptibility to various common bacterial and viral infections in children. We have now designed genetic tests by which we can determine the frequency of these defects in the pig population. This technology will enable selective breeding of pigs that do not carry the detrimental mutations. If this is successful, the requirements for antibiotics in feed will be reduced.