Landon Getz (left) and Sam Fairburn

February 25, 2025

By Sunitha Chari

University of Toronto researchers have discovered nine new genes used by bacteria to protect themselves against viral infections.

Their findings uncover a new hotspot in the bacterial genome for these protective systems and could have profound implications for the development of new strategies to treat bacterial infections, particularly those that are drug resistant.

“Phages are viruses that naturally predate bacteria,” says Landon Getz, a postdoctoral fellow in Karen Maxwell’s lab in the department of biochemistry at U of T’s Temerty Faculty of Medicine. 

“If we understand the defence mechanisms activated by the bacteria in response to phage infections, we can develop methods to bypass them.” Doing so would make bacteria more vulnerable to phages, which can be used as a treatment for drug resistant bacterial infections.

In a study published in Nature Microbiology, Getz and his colleagues discovered that the genes associated with anti-phage defence in the bacteria Vibrio parahaemolyticus are clustered in a region of the bacterial genome known as an integron.

Integrons are genetic elements that store foreign genes that bacteria have picked up from other bacteria in the environment. These genes can confer a survival advantage to the bacteria — for example, making them immune to certain antibiotics — but their role in anti-phage defences is not well understood.

“We knew that genes associated with anti-phage defences cluster together in bacterial genomes,” says Getz, who received the GSK EPIC Convergence Postdoctoral Fellowship in Antimicrobial Resistance. “When we identified a few known defence genes in the integron, we could hypothesize that we might find new anti-phage defence genes in that region.”

Using bioinformatics, Getz and his co-authors selected 57 genes from the Vibrio integron for their study. They also selected more than 70 different phages to test whether the newly identified defence systems could protect the bacteria from phage infections.

The number of known phages that infect V. parahaemolyticus is small and, Getz says they had to get creative and turn to unusual places.

“Vibrio parahaemolyticus is an important bacterial pathogen that infects seafood and causes gastroenteritis in people when they consume raw or undercooked seafood,” he says. To look for phages that could infect this marine bacterium, the researchers sifted through sediment samples from tanks housing upside down jellyfish and sea dragons at Ripley’s Aquarium in Toronto.

The researchers next used a technique known as phage spotting to determine if a gene provides defence against viral infections.  “We cloned the 57 genes into different bacterial strains and grew them on agar plates,” says Sam Fairburn, co-author on the study and a fourth-year undergraduate student at the University of Waterloo who worked as co-op student in the Maxwell lab for the study. “We then added a drop each of the different phage samples to the plates.”

Fairburn explains that in the absence of an active anti-phage defence, viral infections inhibit bacterial growth and cause a clear zone on the bacterial plate. Through these experiments, researchers identified the nine unique and previously unknown defence genes in the Vibrio integron.

While these  genes provide bacteria with obvious survival benefits, turning them on consumes extra energy, so bacteria activate the defences only in response to specific environmental cues.

“Quorum sensing is the ability of bacteria to listen to each other when they are present in a crowded bacterial environment,” says Getz, who is also co-supervised by Mikko Taipale, an associate professor of molecular genetics at Temerty Medicine.

The researchers discovered that in V. parahaemolyticus, four of the nine new defence systems were turned on in response to quorum sensing.

“Viral infections are a bigger problem for bacteria when they are present in large numbers, so it makes sense that these anti-phage defences are upregulated in response to quorum sensing,” he adds.

Moreover, Getz notes that integrons are found in virtually all Vibrio species and roughly 10 per cent of all bacterial genomes. The widespread prevalence of integrons makes them a promising target for developing strategies to bolster the effectiveness of phage therapy.

“If we target phage defence systems present in bacteria to treat the infection, then we can get around some of the issues with antibiotic resistance and develop novel phage-based therapeutics with applications in shellfish fisheries, and potentially in humans.”