Phage fighters

A new study shows how some viruses can be harnessed to help fight bacterial disease

MANY VIRUSES understandably have a bad reputation as agents of illness. But a new study from Cork highlights how some viruses could be harnessed to help in the fight against bacterial disease.

Bacteriophage or “phage” viruses have a penchant for killing bacteria.

And researchers at the Science Foundation Ireland-funded Alimentary Pharmabiotic Centre (APC) at University College Cork (UCC) and Teagasc in Moorepark have used two phage viruses to attack the bacterium Pseudomonas aeruginosa in lab models of infection.

The pseudomonas bug they are targeting can cause problems for people with cystic fibrosis when it grows in mucus in the lungs, explains UCC-based researcher Prof Colin Hill from the APC.

“People with cystic fibrosis have a genetic mutation which, among other things, leads to a build-up of mucus in the lungs. This mucus is a very good place for Pseudomonas aeruginosa to grow.

“It is an opportunistic pathogen, which can infect body sites which are compromised in some way but normally cannot infect healthy tissues. Such a build-up of pseudomonas in the lungs can reach the point where it presents a real threat to the health of the individual,” he says.

“This can be controlled with antibiotics, but as a result people with cystic fibrosis tend to be on long-term or even lifelong antibiotic therapy, which then increases the risk of antibiotic resistant strains emerging.

“Once this happens the antibiotics become less and less useful. That is why alternatives to antibiotics are attractive.”

So why did phage viruses catch their attention as a potential way to stop the bacteria? “We have long been interested in phage as a problem, in that they can inhibit bacteria used in industry to make fermented foods, or even bacteria used to make pharmaceuticals.

“It was interesting to try to find a way to use them in a beneficial way, rather than purely see them as a problem,” says Hill.

“Combined with the rise of antibiotic resistance and the lack of new antibiotics, it seemed an obvious thing to try. It has been done in Russia for many years.”

The researchers isolated two new phage viruses from sewage from a wastewater treatment plant, analysed them and set them to work on P.aeruginosa. "We were able to 'find' new phage that are able to kill P.aeruginosa," says Hill, who worked on the project with Prof Paul Ross at Teagasc in Moorepark and researchers at Cork Institute of Technology and McGill University in Canada.

“We used an animal model of infection to see if they could work in the lungs, and we used a cell line derived from an individual with cystic fibrosis to mimic the cystic fibrosis lung.”

The study took an interesting approach to track the fate of pseudomonas – they made the bacterial cells glow.

“By introducing genes from another bacteria which emits light naturally, we were able to make strains of pseudomonas which emitted light,” explains Hill.

“This light can be followed in real time. So we can look at the growth and death of pseudomonas as it happens, not by plating and counting colonies, but by using really powerful cameras to pick up the light.”

And what they saw was encouraging, both in the cell-line and lung infection models. “Happily, the phage worked really well in both situations in that they could completely clear the infection in both instances,” says Hill.

“We then tested against a range of strains isolated from infected lungs, and they worked in every case.”

The findings, published recently in the journal mBio, were seen in the lab, and progressing to a therapy would require “significant investment” as well as time, notes Hill.

“If money was no object we would go straight into human safety testing to ensure that the therapy will cause no health issues in its own right, then into clinical trials, and then to the clinic,” he says. “This takes time, three to five years, but there are no shortcuts.”

However, phage viruses have some neat aspects that Hill reckons make them attractive as potential treatments – not least that when they infect a bacterial cell, they make lots of copies of themselves.

“The key thing about phage, which gives them a lot of potential, is that they are self-replicating when the target bacterium is present,” he says.

“So if you give them to someone with no infection, nothing happens. But if you give them to someone with an infection, the treatment multiplies up until the infection is eliminated.

“This aspect, combined with their overall safety, gives me hope that they will have a significant impact in this and other diseases.”