Bacteriophages; what are they?

A bacteriophage is a kind of virus that feeds on bacteria (phage means to eat in Greek). They're probably best known for their weird tailed shape, though not all of them look like this:

Electron micrographs of bacteriophages
Some phage micrographs from four different phage families. (Source paper on ResearchGate)

Bacteriophages are pretty much everywhere, including in our bodies. However, they're ultra-picky eaters and will ignore human cells and most other bacteria. This makes them perfect for targeting bacterial pathogens in our bodies, giving us a medical treatment known as phage therapy or phagotherapy.

Deadly Duo

Humans and phages are two very deadly groups of creatures, but they don't really do anything to each other. The real power comes when they collaborate. (Or rather, when us humans abuse the laws of nature through phages for our own gain.)

In phagotherapy, a medical provider injects bacteriophages into the patient's body as a counter to antibiotic-resistant bacteria that's making them sick. It seems to come with very little side effects and is extremely effective if done correctly. Research slowed as antibiotics started to gain popularity, but now that we've accidentally made things harder for us, researchers are picking up the pace!

But bacteria will evolve and become resistant to phages, too. What will we do about it? Instead of just throwing in whatever works, one solution is to selectively breed the phages to target the specific trait(s) that make them resistant to antibiotics in the first place. If the bacteria evolve to remove the trait(s) to keep safe from the phages, they'll become susceptible again—this is what's called an evolutionary tradeoff.

A Brief History of Phages

We had hints about the existence of phages back in 1896, but they were only properly noticed in 1915 and independently again in 1917. They showed up as "glassy and transparent zones" of dead bacteria on a petri dish. While the 1915 publication by F. Twort listed a few possibilities, the second one by d'Herelle immediately announced them as bacteriophages—he'd seen this phenomenon before, but didn't know the cause until now—and as you probably know by now, he was right.

Scientists quickly started researching its potential as a medical treatment, but the specificity of their targets could pose a problem. Meanwhile antibiotics were on the rise, and eventually they replaced phage treatments in many countries. Some ex-Soviet countries never really dropped it though—to this day, Georgia is the world center for phage therapy.

Thanks to our overuse of antibiotics and natural selection, we've accidentally engineered some strains of bacteria to become immune to many of our treatments. This is why scientists internationally have been turning to phages again. And now that our tech has improved, we can make far better "phage cocktails" to deliver to patients! We still have a ways to go, but we may see more widespread use of this therapy in the coming years.

More recently, George Smith developed a method known as phage display. He explained the idea in a lecture about the 2018 Nobel Prize: in short, there's a certain type of phage with proteins that partially show up on its surface. If you insert some extra DNA next to that part of the gene, the resulting extra piece shows up as an extension of the main protein. Filter these out and feed them some bacteria, and you'll get a huge supply of them by morning!

There's not much else to say about it without further confusing 90% of the remaining audience, so I'll end it here for now.

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