The use of metagenomics to develop mitigation strategies for Escherichia coli O157:H7 colonization in cattle.

Using functional genomics to study cattle rumen and large intestine metagenomes, we will identify novel bioactive compounds for the control of E. coli O157:H7 and other pathogens in cattle and develop innovative mitigation strategies based on a greater understanding of the microbial ecology of cattle shedding of E. coli O157:H7.

Date of Submission:	July 14, 2010
Total Budget:	$500,000
Total Amount Requested from Genome Alberta/ALMA (less than $500k):
Project Duration:	3 years

Project Leader(s)	Brent Selinger University of Lethbridge 4401 University Drive Lethbridge Ab T1K 3M4	Tim McAllister Agriculture & Agri-Food Canada Lethbridge Research Centre P.O. Box 3000 5403 -1st Avenue S. Lethbridge, Ab T1J 4B1
Co-Applicant(s)	Name	Affiliation
	Alan Dobson	University College Cork, Cork, Ireland
	Ronan Loftus	IdentiGEN Canada Ltd, Edmonton, AB

Project Summary
Escherichia coli O157:H7 is a major food borne human pathogen causing disease worldwide. Cattle have been recognized as the primary reservoir for this pathogen. Healthy cattle transiently host E. coli O157:H7 in their gastrointestinal tract, with the bacteria mainly residing in the rectum of the large intestine. The shedding load and frequency of E. coli O157:H7 shedding varies greatly among individual cattle. The term “super shedder” has been applied to cattle that are transiently high shedders of E. coli O157:H7. These animals are estimated to account for greater than 80% of the E. coli O157:H7 shed in feces of cattle. Targeting super shedder cattle for mitigation strategies has been proposed as a means of reducing the incidence and spread of E. coli O157:H7 to pen-mates and the feedlot environment.

The incidence and shedding load of E. coli O157:H7 is most certainly affected not only by characteristics of the host animal but also by the microbial community (i.e., bacteria, fungi and protozoa) inhabiting the gastrointestinal tract (GIT) of the host animal. The gastrointestinal microbial community is critical to host health and well being. The normal microbiota not only produces necessary nutrients (i.e., vitamins and short chain volatile fatty acids) but also has been implicated in the development of a healthy immune system and exclusion of enteric pathogens. The mechanisms for competitive exclusion include competition for resources and production of bioactive compounds that inhibit colonization and growth of these pathogens.

We hypothesize that the super shedding condition is a result of intestinal imbalance and that a healthy normal microbiota prevents E. coli O157:H7 colonization of the cattle intestinal tract through competitive exclusion involving the production of bioactive compounds inhibiting colonization and growth. The objectives of this proposal are to identify and develop:

1. Novel bioactive compounds for the control of E. coli O157:H7 and other pathogens in cattle
2. Innovative mitigation strategies based on a greater understanding of the microbial ecology of cattle shedding of E. coli O157:H7.

To accomplish these objectives, we propose to apply functional genomics to the study of the cattle rumen and large intestine metagenomes.