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Using Bacteriophages To Put The Brakes On Escherichia Coli O157: H7

Escherichia coli 0157: H7was first identified as a human pathogen following two outbreaks of gastrointestinal illness in the United States associated with undercooked hamburger patties in 1982 and has been known as hamburger disease ever since. Most strains ofE. coliare harmless inhabitants of the gastrointestinal tract of humans and other warm-blooded animals, but pathogenicE. colistrains, such asE. coli 0157: H7can cause serious bloody diarrhea and in severe cases kidney disease and even death.

The disease is particularly prevalent in children under 10 and in the elderly or immune-compromised individuals, but anyone can potentially acquire disease. Since its discovery in the United States it has been documented in over 50 countries across six continents. It costs the Canadian economy about $100 million each year and occurs at a rate of about 2.3 cases per 100,000 people in Canada.

Outbreaks linked to vegetables, fruit juices and other mammals and insects indicate thatE. coli 0157rapidly disseminates within the environment, but beef cattle are thought to be the primary reservoir of the pathogen.

Within the beef cattle population, our work has documented that individual cattle known as super shedders (cattle that shed greater than 100,000 bacteria per gram of feces) are key in the transmission of this bacterium among cattle within the feedlot and to the surrounding environment.

Bacteriophages are viruses that specifically infect and kill bacteria, and our team has established a collection of phages that are extremely specififor killingE. coli 0157,thereby avoiding the disruption of beneficial bacteria. Phages invade the bacterial cell, commandeer the cellular machinery of the host and self-replicate, culminating in lysis or destruction of the host cell and the release of progeny that can in turn infect more of the host bacteria.

Our team has specifically selected a collection of phages from commercial feedlots and dairies that are capable of killing a wide range ofE. coli 0157.These bacteriophages also release large numbers of viral progeny upon lysis, thus increasing their chances in coming in contact with and killing the targeted host. Phages may be particularly suited for controllingE. coli 0157: H7in super-shedders where there are large numbers of hosts for them to infect.

Work in our laboratory has already shown that feedlot cattle that harbour bacteriophages, lack or have lower numbers ofE. coli 0157: H7and one of our objectives is to develop management practices that promote bacteriophage proliferation.

To be effective, phages have to come in contact withE. coli 0157: H7and as phages lack motility this is essentially a random event. The likelihood of this event occurring is logically higher in super-shedders where we have measured as many as one billionE. coli 0157: H7per gram of feces.

Bacteriophage therapy is not a new science and was a major field of study prior to the advent of antibiotics in the 1930s. Recent concerns about the emergence of antibiotic-resistant bacteria have led to revitalization in the interest of using bacteriophages to target specifibacterial populations.

Bacteria can also develop resistance to bacteriophages and we have witnessed this adaptation in our own research, where some strains of resistantE. coli 0157required 1,000 times more phages in order to kill them. Consequently, we have employed the strategy of using a cocktail of four or more phages in our therapeutic studies as a means of reducing the likelihood ofE. coli 0157becoming resistant to all phages within the mixture.

In our challenge studies usingE. coli 0157: H7,we have found that inoculation with bacteriophages can lower the number of 0157 shed, but that the animals frequently reacquireE. coli 0157: H7either from the hides of pen mates or from the pen floor. Selecting phages that exhibit greater persistence in the environment may be a means of overcoming this limitation.

Bacteriophages have already been approved in the United States for the control of Listera monocytogenes on meat and meat products. However, using phages to control a target bacterium on the surface of meat is far less complicated than attempting to use this same approach to controlE. coli 0157: H7within the digestive tract of cattle and the farm environment.

We are presently undertaking whole-genome sequencing of a selection of isolates from our phage bank in an effort to define those factors that optimize their success against the targeted host. Understanding the nature of the interactions between bacteriophages and their host could be the key to developing phage formulations that are effective in both the animal and the farm environment.



Our team has selected a collection of phages from commercial feedlots and dairies capable of killing a wide range ofE. coli 0157

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