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Battling bad bugs

Scientists fight antibiotic resistance by using synchrotron to study scab disease in potatoes.
Bugs

Scientists fight antibiotic resistance by using synchrotron to study scab disease in potatoes.

In the ongoing war against antibiotic resistant bacteria, a change in battle tactics may prove effective for controlling a common disease of plants and potentially other toxins that affect humans and animals.

Although bacterial toxins cause serious, often deadly diseases, 鈥渂acteria aren鈥檛 trying to be nasty,鈥 said Dr. Rod Merrill, Professor of Molecular and Cellular Biology at the University of Guelph. 鈥淭hey鈥檙e hungry and looking for food, and we鈥檙e often the food.鈥 He added that 99 per cent of bacteria are helpful 鈥 like gut flora 鈥 so the battle is against the remaining one per cent.

The usual approach is to develop antibiotics 鈥渢hat kill the bacteria but not us, or the plant, or the animal,鈥 stated Merrill. However, bacteria mutate quickly, as quickly as every 30 minutes, which leads to antibiotic resistance. 鈥淎nd unfortunately, the pipeline for new antibiotics is empty.鈥

The approach that Merrill and his research group are pursuing is an anti-virulence strategy 鈥 finding or designing small molecules that inhibit the tools bacteria use to colonize the host and create infection. 鈥淚f we can put a lock on their weapons, they can鈥檛 get food and will move on so there鈥檚 not the same pressure to mutate. We鈥檙e going with this approach because we think it鈥檚 time to change up tactics.鈥

To validate the concept, Merrill turned to a bacterium called Streptomyces scabies that causes the common scab disease in root and tuber vegetables like potatoes and carrots. The disease creates lesions on the vegetables, making the food unsightly and unsuitable for sale.

鈥淧otato is the most important vegetable crop in Canada and the fourth largest crop in the world,鈥 said Merrill, who grew up on a beef farm in southern Alberta. Since there is no treatment, common scab has a significant economic impact for producers, reduces the arable land available for growing because it persists in soil, and creates potential food security issues for consumers.

Merrill and his team used the Canadian Light Source (CLS) at the University of Saskatchewan to study a protein toxin produced by the Streptomyces scabies pathogen. The CMCF beamline at the CLS helped them to generate a 3D structure of the toxin and to identify the active-site of the protein, which he described as 鈥渢he mouth of the wolf.鈥 The toxin uses its active-site to bind and cleave cellular molecules which damages the healthy host cells. It was critical information in finding a small-molecule inhibitor 鈥渢o muzzle the monster.鈥

However, there is still further work required to demonstrate that the toxin inhibitors will work to neutralize the Streptomyces scabies pathogen. Once the anti-virulence approach has been established in the laboratory environment, the questions become, 鈥渋s it practical, at what cost and will it work in a crop field environment? We haven鈥檛 yet demonstrated that it will work in cell cultures, but ultimately, we hope to work with agriculture specialists who can make a viable product to help farmers. I would love to see this go to the next level.鈥

Merrill believes the anti-virulence strategy in the fight against bacterial infections has potential applications far beyond diseases of root vegetables, including infections in humans, an area to which he devoted 15 years of his career.

Human medical research is rewarding, but finding trigger locks for the weapons of pathogens that affect animals, plants and his current specialty, honey bees, offered the opportunity to return to his agricultural roots.

鈥淚t鈥檚 very fulfilling working with the bee-keeping industry, and on other crop and animal diseases.鈥

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