By Alice McFarlane

Researchers discover new antimicrobial resistance gene in livestock disease treatment

Feb 23, 2023 | 3:24 PM

MELFORT, Sask. – Researchers have discovered how a previously overlooked gene is involved in antimicrobial resistance which is a growing global issue that threatens the health and welfare of both humans and animals.

The work at the University of Saskatchewan (USask) found the gene encodes for an enzyme named EstT is capable of turning off macrolides, a class of antibiotic drugs commonly used to treat disease in cattle and other livestock.

Tylosin, tilmicosin and tildipirosin are some antibiotics classed as macrolides.

Dr. Poonam Dhindwal said veterinarians rely on these drugs to treat illnesses in cattle such as bovine respiratory disease and liver abscesses as well as other diseases in livestock and companion animals.

“There’s a possibility that the drug will not work because of the presence of the gene,” Dhindwal said.

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Antibiotics are becoming less effective due to the global spread of antimicrobial resistance. Based on 2019 estimates, more than 1.2 million human deaths were caused by drug-resistant infections. Antimicrobial resistance genes (ARGs) are mobile genetic elements that can pass between micro-organisms and help to accelerate resistance.

The USask research team made the discovery after analyzing bacteria collected from watering bowls at a western Canadian beef cattle feedlot.

The research was led by assistant professor Dr. Tony Ruzzini in collaboration with Dr. Murray Jelinski.

“[Our discovery] adds one more piece to the puzzle,” Jelinski said.

Scientists have previously identified the existence of this gene that’s commonly found in many animal pathogens and their microbiomes, but its purpose remained a mystery.

Ruzzini said the research team discovered the gene can break the ring structure of the antibiotic through hydrolysis which is a chemical reaction caused by water.

“If you break the ring or you open the ring with water, then you disrupt the active shape of the antibiotic. So, it no longer has a high affinity for the target,” Ruzzini said.

Once the gene destroys the antibiotic’s structure, the drug is no longer able to work as effectively in treating an illness.

The team found the gene in a cluster with three other ARGs. Ruzzini said this was the first clue that it could be involved in antimicrobial resistance. Once the team identified the gene, team members worked to clone it and test it against a panel of many antibiotic drugs from different classes.

“This gene, even though we found it in an environmental organism, it is also present in pathogens that are responsible for causing bovine respiratory disease (BRD),” Ruzzini said.

The team’s work should be of interest to all researchers in both human and animal health fields who are studying antimicrobial resistance.

Ruzzini added that his research team is continuing to learn more about how EstT works.

“As AMR surveillance systems rely more on molecular tools for detection, our knowledge of this specific gene and its integration into those systems will help to better inform antimicrobial use,” Ruzzini said.

The Saskatchewan Health Research Fund, Saskatchewan Agriculture Development Fund, the Beef Cattle Research Council, and the Mitacs Globalink Internship program supported the research.

The findings were published online last week in Proceedings of the National Academy of Sciences (PNAS) journal.

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alice.mcfarlane@pattisonmedia.com

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