Photo Credit: Emily Brown

Bacteriophages, also known as ‘phages,’ are the most common lifeform on the planet. They are constantly hunting for bacteria to infect and kill. What if we could harness these tiny microbes to help us in our fight against harmful, disease-causing bacteria? On this episode of The Show About Science, Ben Chan, from Yale University, joins Nate to explore the potential of phages in treating human infections amid the declining effectiveness of broad-spectrum antibiotics.

If you’re interested in collecting phage samples, you can email Ben at b.chan@yale.edu for further instructions on how to safely prepare and send your samples.

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Transcript

Nate: There’s a microscopic fight that’s been raging all around us, and it’s been going pretty much since life began on Earth.

On one side, we have bacteria, those small single-celled organisms who live nearly everywhere on the planet.

And then on the other side, we have bacteria’s mortal enemy, the bacteriophage.

They are everywhere, even more prevalent than bacteria, and their mission, to infect and destroy.

Ben Chan: Bacteriophages are the viruses of bacteria and only bacteria.

Nate: This is Ben Chan, a research scientist from Yale University.

Ben Chan: And if they weren’t here, this world would be a pile of bacteria in a couple of days, because every day, almost half of the bacteria on the planet are killed by bacteriophages.

Nate: These microscopic phages are keeping our world in balance.

But it’s bigger than that.

Because humans have also been engaged in a battle against harmful bacteria.

And we’re losing.

Because our primary weapon in this fight, antibiotics, well, they’re starting to fail us.

On this episode of the show, we talk to Ben Chan about whether or not phages, the enemy of our enemy, could possibly be our friend.

I’m your host, Nate.

This is The Show About Science.

And that’s after the break.

Nate: And we’re back with Ben Chan.

Ben Chan: Yeah, thanks for having me.

Nate: Yeah, I’m really excited that you’re on the show with me.

And so just to start, I think it’d be good if we got a picture in our minds of what these phages look like.

Ben Chan: Okay.

Nate: So when you think of a human virus, you would probably imagine this hexagon sort of thing with little lines poking out of it, maybe with an evil grin on its face or something like that.

Ben Chan: Yeah.

But what do bacteriophages look like? And how is that different from viruses that infect us?

Ben Chan: Yeah, so bacteriophages are really diverse.

So there’s a whole bunch of different shapes and sizes of them.

But the stereotypical bacteriophage has this capsid, which is the top.

It looks basically like any other virus, like the ones you’re describing with the evil grin.

Maybe these ones are smiling, and they have a little tail that comes out of that capsid, and then little tail fibers, which are like little legs hanging off the bottom of that.

So they kind of look like little aliens.

Nate: And how do we even find phages? Where can we get them from?

Ben Chan: So bacteriophages are everywhere, really.

If there are bacteria there, which bacteria are everywhere, there are bacteriophages.

Since they outnumber bacteria 10 to 1, they can be found in like almost any environment.

However, finding the right bacteriophage can be a little difficult because you have to find the bacteria you’re trying to kill, and only where that bacteria exists will you find phages.

Nate: So you find your own samples of these bacteriophages.

Where do you typically go to find different ones, and what are you trying to accomplish by finding all of these different samples?

Ben Chan: Yeah, so the bacteria that I frequently encounter in infections, you know, we have several, but they’re all human pathogens.

And so when I’m looking for bacteriophages, I look for where the bacteria might be.

And so these bacteria are in, you know, human samples, so they’re like in blood or wherever the infection is, but also in sewage because, you know, everything that comes out of us ends up in a sewer somewhere.

So it’s like a giant pool of bacteria and bacteriophages.

So I end up getting a lot of sewage samples.

Nate: So what is your actual collection process like for these bacteriophages?

Ben Chan: Yeah, so collecting phages is actually super easy.

It’s really, we just take these little tubes and we just scoop up sewage.

So sometimes there’s like a, you know, we have to use like a giant rope with a bucket to throw it out into a puddle of sewage.

But other times if we’re closer, we just basically dip the tube in and collect it.

Super easy, a little bit gross, but really it’s just scooping up water.

Nate: Yeah?

Ben Chan: Yeah.

Nate: And then once you’ve collected the phages, what do you do from there to like find out which ones you have?

Ben Chan: So once we have a sewage sample, we filter it because we want to get rid of like all the dirt and the gross stuff and the bacteria.

And then we have basically a water sample that has only viruses because they’re smaller than most organisms.

Then we drop the bacteria on a Petri dish.

So it’s basically just a lot of bacteria.

Then we take this water that has a little bit of phages in it and we basically put a droplet of it on the lawn of bacteria.

And then we incubate it in the incubator and then we look at it the next day.

And if there’s a clearing where that water droplet was, then it suggests that there was a phage that basically replicated and killed all the bacteria in that area.

But to actually see them, we have to use an electron microscope because they’re super small.

Nate: Now that we’ve kind of got a picture of what these phages look like, we need to understand the big problem that makes them so valuable to us at this moment.

And that problem is antibiotic resistance.

So how is it that the more we use our antibiotics, the more obsolete they become?

Ben Chan: So that is a very important question.

So a lot of times, you know, you get sick, you get a bacterial infection, we normally would use antibiotics to treat that.

But a lot of these bacteria are becoming more and more antibiotic resistant because, well, there’s so many reasons for this.

But the first is that it’s just evolution, right?

So if somebody is full of bacteria causing an infection, we use one of these broad spectrum antibiotics.

If there’s any mutation in that population that allows them to be resistant to the antibiotic, that individual clone is going to survive and then it’ll kill off all the bacteria except that one and then that one will grow back up and take over the population.

And then so you’ve evolved antibiotic resistance.

But I think another way antibiotic resistance is becoming a problem is that when we use antibiotics and they work effectively, they kill off the bacteria that’s causing the infection.

However, because they’re like a broad spectrum, and they can kill many types of bacteria, other bacteria in the environment or in the body that are not causing disease, but are like, you know, commensal or environmental or just hanging out, we can actually put selective pressure on those bacteria to evolve resistance.

And the problem with that is that sometimes these bacteria carry the genes for antibiotic resistance, even though they can’t cause an infection, but they can pass those genes like they can give those genes to other bacteria that can cause disease.

And so we have all these bacteria that can pass these genes to infectious bacteria.

Nate: So the bacteria that survive are the ones that get to reproduce.

And since we’re targeting them with antibiotics, the only ones that will be able to reproduce are the ones that can withstand a round of antibiotic treatment.

So essentially what we’re doing is we’re breeding bacteria that can withstand the antibiotics the more we use them.

Ben Chan: Exactly, yeah.

Nate: And then if these harmful bacteria then get this antibiotic resistance gene, what can they then go around and do to our bodies if we can’t treat them?

Ben Chan: Yeah, so if they’re causing the infection and they have resistance to, you know, all these antibiotics, it’s of course a problem, right?

In that you’d have to use newer and newer antibiotics if they’re available, and eventually if the bacteria is resistant to all antibiotics, then you have a really serious problem where you’re going to need some alternative or you’re going to get really sick and in some of the really, really bad cases you could die.

And so that’s why we’re trying to investigate new antimicrobials, new antibiotics, new approaches such as phages.

Nate: So in our fight against bacteria, the one we started losing with antibiotics, phages are kind of a new weapon.

And when a phage finds a bacteria, and it is the type of bacteria that they would infect, what happens from there is really interesting.

Ben Chan: Yeah, so as the phage is, you know, sort of bouncing around in the environment and it bumps into a bacteria that it can infect, it uses, often but not always, it uses these little feet at the bottom to stick to the bacteria and then it injects its DNA or RNA and then basically hijacks the bacterial metabolism, it takes over the bacteria and then makes copies of itself.

And then once those new versions of the virus are ready, it explodes the bacteria and each one of those little guys goes out and tries to find a new bacteria to infect.

Nate: Wait, okay, how does one little phage cause a whole bacteria to explode?

Ben Chan: Yeah, so the phage, once it injects its DNA into the bacteria, then that DNA uses the bacterial metabolism and copies itself and then it translates into bacteriophage parts.

So then you have a bunch of parts floating around in the middle of the bacteria, which is, it’s basically dead, right?

Cause it doesn’t have any of its own DNA left cause they all got chopped up by the phage.

And then it assembles those phages particles.

So then you have a bunch of phages ready to go, you know, anywhere from three to 5,000 particles are jammed inside of this bacteria ready to go.

And then once they’re ready, it produces an enzyme.

It’s a lysin that basically cuts apart the cell wall and then the viruses fly out.

Nate: Okay, that’s pretty cool.

Ben Chan: Yeah.

Nate: So once phages are introduced to this antibiotic resistant bacteria, what would happen if they ended up developing a resistance to bacteriophages too?

Ben Chan: So that definitely happens and that’s one of the key pieces of the research we do here because if you throw anything at bacteria, they’ll figure out a way to become resistant.

So antibiotics, they evolved resistance.

And then since phages have been around, basically since they’ve been bacteria, they’ve been a long time for bacteria to evolve ways to become resistant to phages because like, as I was saying, almost half of the bacteria on the planet are killed every day by phages.

So there’s a huge selective pressure to evolve ways to be resistant to phages.

And so in our case, we’re looking for phages that select for antibiotic sensitivity.

So in a way, we’re sort of trying to push the selective pressure in the opposite direction to resensitize them to antibiotics.

Nate: So what you’re saying is we’ve been using antibiotics so much that bacteria have been forced to evolve in order to survive.

And now by using phages, we’re trying to push them in the opposite way to get them to evolve resistance to phages instead of antibiotics so that then we can use those antibiotics again.

Ben Chan: Yeah, exactly.

Nate: And then what do these bacteriophages do once they’ve run out of bacteria in a certain area to infect?

Ben Chan: So then because they’re just viruses and they’re basically just a protein coat and DNA, they don’t have any of the machinery that bacteria have or other cells have to repair.

So basically, if there’s any damage to the DNA from like radiation or if they’re just bouncing around and pieces break, they just fall apart.

So they just eventually disappear.

They’re self-limiting.

So in an infection, when we treat it, if it kills all the bacteria and there’s no bacteria left, then the phages just fall apart.

Nate: And while they’re doing that, they wouldn’t do any harm to human cells if we end up putting them into our bodies, right?

Ben Chan: Yeah, that’s right.

That’s one of the things that makes them a really appealing antibiotic is that they don’t have any ability to infect human cells.

Nate: And so what are we going to try to do with phages?

Like what’s the end goal with them?

Ben Chan: Well, so there’s a few.

So in our group here, we work mostly with chronic infections.

So those are infections that have been in the person for months or years.

And so our goal is to try and manipulate that infection so it becomes antibiotic sensitive again.

But there are others that are trying to cure the infections completely, which would be great if we could do that.

And so that’s sort of the end goal is to make bacteria antibiotic sensitive or less able to cause disease or to eradicate the infection completely.

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Nate: Just to wrap things up, do you have any advice for kids who are interested in learning more about phages?

And could they collect some sewer samples to send to you?

Ben Chan: Yeah, well, yes, of course.

Maybe not sewage, though, because that can be a little bit of a biohazard.

But phages are everywhere, right?

So they’re in water samples, like they’re in lakes, ponds, rivers, compost.

You can work with solid samples, too.

And yeah, of course, anybody could sample and send something in would be more than happy to look for phages.

Nate: OK all you phage hunters, go out and collect your samples.

And I’ll put Ben’s email address in the description so you can reach out to him directly and learn how to ship those samples safely.

Ben Chan: Cool.

Nate: All right, thank you for being on the show.

Ben Chan: Yeah, thanks for having me.

Nate: There you have it, folks, the show about science is complete.

Music on today’s episode was produced by us with additional music by Epidemic Sound.

And our theme song was written by Jeff, Dan, and Theresa Brooks.

Additional production and editing support comes from Tim Howard in Berlin.

[SPEAKING GERMAN]

All right, Dad, you can shut the recording off.

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