A new study shows how bacteriophages can deliver a one-two punch to drug-resistant bacteria.
Image: WikiMedia Commons
Imagine a virus that you inject into your body to hunt down bad bacteria, deposit its DNA, and explode the bacteria from the inside out, ridding your body of infection without wiping out good bacteria in the process.
It sounds futuristic, but it's actually a very old technique for fighting bacterial infections, and many researchers now believe it will be an indispensable tool in the fight against antibiotic resistance.
Meet bacteriophages: viruses that evolved to target specific species of bacteria as their hosts. They're biologically incompatible with any organism other than their bacterial host partner, which means they can't infect humans, they just hunt down the bacteria making us sick and destroy them.
Phages were discovered in 1917. In the early 20th century, phage therapy was used to treat all kinds of bacterial infections, according to Daniel Nelson, an assistant professor at the University of Maryland who studies bacteriophages. But after penicillin was discovered, that changed.
"Everything went to antibiotics and phage therapy research stopped in western countries," said Nelson.
In recent years, antibiotic effectiveness has been dropping, with more and more bacteria developing resistance to one, or sometimes many, antibiotics. There are a lot of reasons for this, including overuse of antibiotics in agriculture, but the fact remains that in some cases we're losing even our last resort treatment for some really nasty and occasionally deadly bugs.
But we have bacteriophages, so problem solved, right? Not quite. Bacteria is able to develop resistance to phages too, and often much faster than they develop resistance to antibiotics. Luckily, a paper published Thursday in Scientific Reports shows we might be able to use that fact to our advantage.
"Bacteria have been exposed to phages for as long as there have been bacteria, so they've had a long time to develop efficient ways to avoid phage infections," Benjamin Chan, an associate research scientist at Yale and lead author of the study, told me. "So in our study, we were capitalizing on that."
Chan and his colleagues identified a bacteriophage that infiltrates its bacteria—in this case Pseudomonas aeruginosa, a multidrug resistant pathogen—by attacking a specific protein exposed on its surface.
Unfortunately for the bacteria, that's also the protein the resistant bacteria uses to pump antibiotics out before they can do any damage. So the bacteria is left with a difficult choice: evolve to resist the phage, or evolve to resist antibiotics, but it can't be resistant to both. It puts pressure on the bacteria to evolve back to a state where it's sensitive to antibiotics.
Or, that's the idea, anyway. The researchers tested the bacteria against a number of different antibiotics to see if it was more sensitive after being exposed to the bacteriophage.
According to the paper, the bacteria was significantly less resistant—in one case 100 times less resistant—to antibiotics after the phage therapy trials. In a clinical setting, this kind of phage therapy would be delivered to target the infection, Chan said. So if you have a bacterial infection in your lungs, you'd inhale the bacteriophage treatment through an inhaler. It would also be combined with antibiotic treatment to ensure no matter which resistance the bacteria has, you'll have a good chance of wiping out the infection.
Chan said the results were promising but more works need to be done. He doesn't consider phage therapy our best bet in fighting antibiotic resistance (it's just "a bet," he joked) but believes using phages in different, targeted ways will be an important tool going forward and in some cases may even be used to replace antibiotics. Nelson echoed this sentiment and said Chan's research is just one way phages might be used.
"There are people that use phage proteins. My personal research is using enzymes that phage produce. People are using phage to deliver CRISPR/Cas9 [for gene editing]," Nelson said. "These are all valid and you're going to see more and more of this in the future."