The Story of ASSETS: Fighting Antibiotic Resistance in Livestock

Infectious diseases like Bovine Respiratory Disease can impact cattle. A team of researchers based at the University of Saskatchewan, the University of Alberta, Agriculture and Agri-Food Canada, and Prairie Diagnostic Services have made significant progress using genomics to better detect infection and treat these diseases. The benefits could be substantial.

Canadians, like much of the rest of the world, eat meat. Lots of meat. In 2021, the world consumed more than 320 million tons of the “big meat three”: poultry, pork, and beef.

Today, more than ever, the global human population relies on beef as a sustainable and nutritious source of protein.

According to Statistica, the 140 billion or so pounds of beef consumed in 2021 was about 30% more than what was eaten at the turn of the century. As you might imagine, beef production in Canada is a lucrative business. According to the Canadian Cattle Association, the beef industry generated nearly $22b for the national economy last year on more than 60,000 farms.

With so many people dependent on beef production and the importance of the industry to food security, infectious disease is an ongoing threat.

Among infectious diseases, bovine respiratory disease (BRD) is considered the leading cause of morbidity and mortality within the cattle industry. While potentially deadly if left untreated, antimicrobials (antibiotics) are available to battle infections.

The use of antibiotics, however, raises the specter of an emerging and serious challenge for beef producers. For years scientists and medical experts have voiced heightened concerns about the rise of antibiotic resistance in humans. Moreover, the use of antibiotics has led to more infections in cattle becoming resistant to treatment, just like in human populations, risking future challenges for disease control.

“Antibiotic resistance surveillance and research to inform best practices for antimicrobial use and disease management have been priorities for the beef industry for more than twenty years,” said Dr. Cheryl Waldner, professor at the Department of Large Animal Clinical Sciences at the University of Saskatchewan. “There is increasing pressure to ensure that antibiotics are used prudently in all sectors, including agriculture, to preserve their effectiveness to protect both animal and human health.”

Waldner is the co-lead for Genome Prairie’s Genomic ASSETS (Antimicrobial Stewardship Systems from Evidence-based Treatment Strategies) for Livestock project, which examines improved strategies to combat BRD.

Launched in 2019, ASSETS is developing a genome-based approach to accurately identify individual calves with bacteria that can cause BRD. The project has developed precision diagnostic strategies to allow veterinarians to test calves for bacteria that cause pneumonia and antibiotic resistance, limiting options for treating the disease.

“The tools developed by ASSETS will better inform prudent antibiotic use for groups of sick animals,” said Waldner. “Beef cattle are typically finished in commercial feedlots before processing. Most calves entering the feedlot are relatively immunologically naïve and are brought together from several different sources providing an opportunity for disease transmission,” said Waldner.

“This creates a situation similar to what we see with our kids in daycares and classrooms. We are mixing individuals from different sources with different exposure to infectious diseases. We see similar respiratory outbreaks in feedlots as in classrooms or daycares.”

“In the feedlots, antibiotics are crucial for controlling disease progression because left untreated, bovine respiratory disease can have severe health and welfare impacts. By identifying bacteria and viruses in cattle arriving at feedlots, we can improve vaccination and disease management recommendations and reduce the risk of respiratory disease and the need for antimicrobial treatment.”

Cattle are a particularly challenging and vulnerable species. One of cattle’s leading contributing factors to respiratory mortality is their lung structure, which makes calves especially susceptible to bacterial pneumonia.

“We most often see viral respiratory illness in people, which most people without pre-existing conditions can recover from without treatment. In cattle, however, respiratory infections tend to be caused by bacteria or viral infections complicated by bacteria. These infections typically require treatment with antimicrobials.”

The ASSETS project, said Waldner, is examining two different diagnostic tools, one of which leverages a “metagenomics” approach to help better identify individual calves who are infected. Unlike conventional (i.e., current) testing, where laboratories look for particular bacteria or viruses, the metagenomics approach provides a more panoramic view of infection.

“Metagenomics casts a fishing net versus using a single line and hook to identify information on infectious organisms. It’s not an individual organism that we’re looking for with this test. With our approach, we’ve cast a very broad net to describe the genomic material we recover from samples.”

“The genomic material tells us not just what bacteria are there, but also crucially identifies antimicrobial resistance genes and specific strains of bacteria more likely to cause severe disease,” said Waldner. “We can also test for a whole suite of viruses with slight modifications to the protocol for processing samples. This gets us much closer to a one-test approach to find out what is causing a problem and how to best manage it, rather than having to know ahead of time what you’re testing for.”

In addition to working towards a one-test approach, the ASSETS project’s progress has been further enhanced by leveraging advancements in genomics technology. The ASSETS team uses Oxford Nanopore sequencing technologies, which allows for real-time DNA and RNA fragments analysis. Waldner said that besides its speed relative to other sequencing options, Oxford Nanopore is continually refining its technology. “We are working with an efficient, comparatively affordable, and increasingly accurate process.”

“With current lab approaches, there are often at least three or four steps and separate tests in the process that examine different diagnostic targets, requiring different sets of equipment and technical expertise,” said Waldner. “Each of those tests has additional costs.”

“For virus testing, we can take the sample, extract the nucleic acid, and enrich and sequence. For bacteria, we get the best results by placing the swab material in a special broth for a couple of hours for the bacteria to multiply, then extract and sequence the DNA.”

Further enhancing the testing process has been integrating robotic technology in an initiative led by Prairie Diagnostic Services (PDS), a non-profit animal diagnostic laboratory based at the University of Saskatchewan. The robotics are programmed to handle much of the preparation work of field samples before sequencing.

“The PDS platform has reduced the time that highly trained technicians need to prepare the samples,” said Waldner. “While extracting DNA and RNA from the samples for our current protocol is still completed manually, everything else after that point is moving towards robotics.”

“Highly trained technicians are crucial to periodically monitor and manage the robotics, but what’s key is they can be doing other things simultaneously. Using robotics to facilitate this kind of sequencing could be a huge game-changer in genomics.”

As the project winds down, with countless pathogen DNA samples taken from calves, Waldner says that the results of collaborative field studies of these new tools will be in the hands of feedlot veterinarians before this summer.

“We will continue to work with our partnering veterinary clinics and get their feedback on how to make the best possible use of these new technologies.”

Photo credits:

Feedlot: Tiago Afonso Omics

Thank you to Genome Prairie for submitting the article and photos.