Bacteriophages Lurk In Your Bathroom, But Don’t Worry

IRA FLATOW: This is Science Friday. I’m Ira Flatow. If you’ve been listening to this program for a while, you know that one of my favorite topics is the bacteriophage, tiny viruses that specialize in hunting down bacteria.

There were big efforts in the former Soviet Union to develop phages as antibiotics or around 100 years ago. But the approach really didn’t catch on here, overshadowed by the rise of conventional antibiotics, like penicillin. But the phages themselves are still out there and might one day help treat disease.

Writing recently in the journal, Frontiers in Microbiomes, researchers report that they have found a whole host of phages that had never been seen before. And where were they? They were lurking in plain sight on things like your toothbrush, your showerhead. Joining me to talk about it is Dr. Erica Hartmann, an Associate Professor in the Department of Civil and Environmental Engineering at Northwestern University in Evanston, Illinois. Welcome to Science Friday.

ERICA HARTMANN: Thank you so much for having me.

IRA FLATOW: Now, these are not something people should be scared of, right?

ERICA HARTMANN: No, absolutely. Bacteriophage are viruses that infect bacteria. They absolutely do not infect people. And while we are very interested in microbes from a human exposure standpoint, we have no reason to think that any of these will actually make anyone sick.

IRA FLATOW: OK, that’s good to start through.

ERICA HARTMANN: Yeah.

IRA FLATOW: Let’s go through your study. You had people send in samples taken from their bathrooms. Why that place in particular?

ERICA HARTMANN: Yeah, so we’re really interested in built environments– our homes, our offices, those kinds of things– for a couple of reasons. One is that it’s where we– in the developed world, we spend most of our time. If you just think about, the course of your day, you spend not so much of it outside. And so this is a really important environment for us in general. And then it’s also an interesting environment.

Because it’s engineered, it’s an environment where we can manipulate parameters. We can change it, and in so doing, we might be able to change our microbial exposures. So that’s one of the reasons we’re interested in the built environment in general and then specifically these samples– so they’re from showerheads and toothbrushes. And so one of the things that’s really important for microbes in terms of being able to survive is the presence of water. And showerheads and toothbrushes are two locations within the bathroom where we thought it would be really interesting to just see who’s there.

IRA FLATOW: And once you’ve collected them, you use genetic tools to separate the various virus types in the samples, right?

ERICA HARTMANN: Yes. So we had extracted DNA from these samples. So we’re only looking at DNA-based microbes, and we wanted to see what types of bacteria were there and then what types of bacteriophage that might be associated with them.

IRA FLATOW: And what did you find?

ERICA HARTMANN: So on the one hand, we found a bunch of things that we don’t really know what to do with, a bunch of viruses that we can’t really say that much about it, except that we can infer that they’re there. And that’s not terribly surprising in one sense because we just know so little about bacteriophage, and there are so many of them out there. It was surprising to me, though, just to see how different every two samples were. So I didn’t necessarily expect toothbrushes and showerheads to look similar, but I thought that maybe there would be more similarities between individual toothbrushes or between individual shower heads. And it turns out that there are just a ton of new and different viruses in each sample.

IRA FLATOW: So one sample from another person– they’re totally different than the viruses that are there.

ERICA HARTMANN: Yeah, more different in the viruses that are there than in the bacteria that are there.

IRA FLATOW: Oh. Well, that’s an interesting thing because if a phage hunts bacteria, usually it’s a one-on-one thing, isn’t it? One phage for one kind of bacteria. But you’re saying that these could be like broad-spectrum viruses, if I hear you correctly.

ERICA HARTMANN: So I don’t know. And I think– this is all speculative. This is all hypothetical here.

But one of the things that I suspect is happening is that the way we have studied bacteriophage in the past– you talked about in Eastern Europe 100 years ago– those methods that they were using 100 years ago are still the methods that have dominated the way we study phage for the last 100 years. So we have these assumptions about how phage work and what they’re like. There are trillions of phage out there, and I think it’s hard to make any general statements about anything with trillions of instances of diversity.

So on the one hand, I don’t know that it’s necessarily one phage, one bacterium. And it could be actually that even though we’re seeing the same bacteria in a lot of places, we see different phage that infect them. So it’s more one bacterium, tens or hundreds of thousands of phage. It’s also possible that there are some phage that can go between different bacterial species, and we just haven’t been using the right methods to detect them.

IRA FLATOW: And that would be good news, wouldn’t it? If you’re trying to develop possibly medicine from the phages, so it might attack many different kinds of bacteria.

ERICA HARTMANN: Yeah, I think there’s a lot of interest in broad or broader-spectrum phage for various reasons. Just from a fundamental biology perspective, understanding what exactly limits or allows phage to infect different hosts is super interesting. And if we can understand how that works, then we could certainly use that to design phage for various applications, including therapeutics.

IRA FLATOW: Where did the bacteria and the phages come from? Did we leave them behind taking a shower or on our toothbrushes?

ERICA HARTMANN: Yeah, so unless you’re doing something different than I am in the shower, I don’t interact with my showerhead that much. And so we suspect that most of the bacteria that are there are actually coming from the water and the premise plumbing system itself. So that’s a one-way street of things coming onto you.

Whereas with your toothbrush, obviously you’re putting that in your mouth. You are definitely depositing a lot of different bacteria onto your toothbrush. But there’s also, on your toothbrush, an opportunity for bacteria from the air in your bathroom, or the water from your faucet, or on your skin because you’re also holding your toothbrush– so lots of different ways for organisms to get to your toothbrush. And so one of the things that I think is super interesting is exactly looking at that biogeography of indoor environments and trying to understand where these bugs come from and where they wind up.

IRA FLATOW: Well, I hate to remind people of the study that showed that the spray from the toilet creating a mist in your bathroom also.

ERICA HARTMANN: So one of the original reasons that we were looking at toothbrushes and the first thing that we did with these samples before we even looked at phage was to look at bacteria. And in part, we were really curious about that. Are there actually toilet aerosols and toilet-associated bacteria that are on your toothbrush? And overwhelmingly, what we see is that the bacteria on your toothbrush come from your mouth. So I wouldn’t be too concerned about it.

IRA FLATOW: Whew, OK. [LAUGHTER] Yeah, because that’s been a big story over the years. Are there any similarities in the samples you see? Are rural ones different from city ones, or ones from the South different from the North or the West?

ERICA HARTMANN: So I think our toothbrush study was underpowered to look at that. The toothbrushes really only came from the Chicago area because that was a small pilot study. From the showerhead samples, the biggest difference that we saw was whether the water came from a well or a municipal system. And that makes sense because there are really different ways of getting, and treating, and distributing water, which, again, goes back to this thought of the built environment is a collection of systems that we can uniquely modify and tune. So if there are maybe specific things that we’re interested in, by thinking about water source and thinking about water distribution systems, we could potentially change them.

IRA FLATOW: Right, right. Now, once you get the phages, how do you figure out what the phages are doing? I mean, do you have to culture them somehow?

ERICA HARTMANN: So 100 years ago, you would have to culture them.

IRA FLATOW: But now we’re in the age of DNA, right?

ERICA HARTMANN: Now we’re in the age of DNA. So what we did– again, we just took DNA from these samples, and using sequencing and bioinformatics– so just trying to interpret that sequencing data, we tried to figure out essentially who those phage would have infected and what types of functions they’re carrying. But we actually couldn’t figure out what most of those putative functional genes or what those functions are. So we can infer a lot just by having the DNA sequence, but there are obvious limitations to that.

And one of the things that I’m really hoping to do going forward is to expand our toolkit for being able to study phage so that we’re not limited to asking questions the same way as they did 100 years ago, and we can actually expand the types of phage we can study. By some estimates, only 1% of bacteria can be cultured. And if you think that there are maybe tens or hundreds of thousands of phage that infect each bacteria, if you’ve only got 1% of the hosts, you’ve only got a teeny-tiny fraction of the bacteriophage.

IRA FLATOW: Wow. Right. Do you think the Soviets, then, were on the right track back then of looking for antibiotics this way?

ERICA HARTMANN: So there are a few things. One is there are billions and trillions of bacteria out there, and they evolve much faster than we do. They have much shorter lifespans and an enormous amount of diversity to sample from. So when we’re trying to think about getting bacteria to do what we want them to do– so in this case, curing an infection– I don’t think there’s a one-size-fits-all approach because there’s this enormous amount of diversity and this enormous potential to evolve.

So I don’t think there is a, quote/unquote, “singular right approach.” I think probably the best thing to do is to have a variety of tools that are based in a variety of systems. And so I think there’s a lot of promise for phage-based control. I think there’s a lot of promise for phage and antibiotic combination therapies. It’s not a question that we’re going to answer and move on from. It’s something that is going to require constant monitoring, and surveillance, and creativity so that we can continue to be able to save lives and protect public health.

IRA FLATOW: But would you say that there is now a renewed interest in phages?

ERICA HARTMANN: Oh, 100%, yeah. It’s a renewed interest, and it’s absolutely justified because the approach that we’ve taken, the antibiotic drugs is no longer working. It’s, I think, motivating a lot of people to be very interested in phage therapies, which is great, but it’s also driving a lot of the tool development and a lot of the sampling efforts to understand these organisms better, which I think is also great.

IRA FLATOW: Mm-hmm. Do you think you can make synthetic designer phage?

ERICA HARTMANN: I, mean, we’re working on it.

[LAUGHTER]

IRA FLATOW: You or just in general?

ERICA HARTMANN: Me and in general. So I think there’s a lot of challenges to engineering phage. We’re getting pretty good at– we, the scientific community, I should say, is getting pretty good at it for certain well-studied phage in certain well-studied organisms.

We’ve used certain elements of phage in molecular biology as research tools for quite some time. But again, there’s this enormous amount of untapped diversity. And so we really need to develop new tools to be able to understand and then manipulate that untapped diversity. And that’s one of the things that I personally am really excited about.

IRA FLATOW: And is that how this study fits in with the designing of phages? Do you collect them just to collect more parts and see what’s useful?

ERICA HARTMANN: That’s one element of it, for sure. So I think before going in and really messing with a system, it can help to understand just how it works and what the basic parameters are that you’re starting with. And so part of what we’re doing is just cataloging things out of general curiosity and trying to figure out what’s out there and how it works and what really does determine the types of microbes that you find on your toothbrush. But then, one of the possible implications from that is exactly having this catalog of functions, and parts, and things that we might be interested in later when we are getting to the point of engineering.

IRA FLATOW: Yeah. I always have a blank-check question I give to my guests, which is, if I had a blank check right here in my back pocket and I was going to give it to you to make, create, or use somehow in your research or to advance the field somehow, what would you do with it? And I guess I’m asking you, where should the money be spent now, these days, on this research?

ERICA HARTMANN: I mean, it’s such a good question. It’s such an open field right now because there’s so much to be learned that I think there are a million different directions you could go with it. I think the method development in particular is really interesting because the better our tools get, the better our methods get, the more interesting questions we can ask.

IRA FLATOW: Let me stop you and ask you, what do you mean by method development? We lay people don’t get that lingo there.

ERICA HARTMANN: Yeah. So 100 years ago, the way you would have studied phage is you would have gotten a Petri dish, and you would have grown bacteria on it, and then you would have added some whatever, like pond water, and looked for what we call plaques, which are holes where the phage have infected the bacteria and killed them. And so it creates a little clearing zone.

And that was that. You can use that. You can use microscopy. And you can try to figure out what these things are. But it’s a very, very limited tool set in terms of being able to really understand all of the different components and really how they work.

And now we’ve advanced with molecular biology. We can do things like DNA sequencing, so we can figure out what the genome sequence of these things are. We have better microscopes. We can see all of the different crazy forms and shapes that they take.

We have new and exciting methods for figuring out how a bacteriophage attaches to a cell and recognizes a host, once it gets into the host, how it hijacks the host’s cellular machinery to replicate itself, what its life cycle is, how it might change over the life cycle, and what all of the different components are within that process. And really, those molecular tools being able to understand step by step what’s happening– that’s what I’m talking about with method development, is really being able to see not just like, ooh, look, I grew something on a plate, but I grew something on a plate. It has 50 different genes, and I can tell you what each of those genes do.

IRA FLATOW: So you don’t have any one pet tool or technique you wish were developed better that you would use your money for?

ERICA HARTMANN: It’s funny. When I first started in research, I was really excited about something called proteomics, which is this way of studying basically all of the proteins that are present in a cell. And I did that for 10 years, and I really loved it. But ultimately, I got to this point in my career where I had to make a decision of, do I keep doing this and get like deeper and deeper into this particular method? Or do I sort of jump fields and expand my toolkit? And I ended up jumping fields.

And in my lab specifically, we don’t necessarily specialize in any one particular method. And part of that is because I want to be able to answer questions from whatever viewpoint is the appropriate one. And being able to use a full toolkit and be able to really figure out what’s the most appropriate way to answer a question, I think, is really exciting. So again, for the field in general, I would not say, oh, there’s one thing that will allow us to completely change everything. I think it’s a bunch of different things that will all come together that– it’s “all of the different hands on the elephant” kind of thing that will allow us to see all of the different parts and then how they work together.

IRA FLATOW: I don’t think I’ll be looking at my toothbrush quite the same way now, although not out of fear.

ERICA HARTMANN: The point that I always try to hammer home is that even though we’re thinking about developing therapeutics, and even though we’re thinking often about fighting infections, the vast majority of bacteria out there are not harmful and possibly even good. So we need bacteria on our skin, and in our gut, and all of those things to actually keep us happy, and healthy, and functional. And we need bacteria in the world to cycle oxygen, and carbon, and nitrogen.

So the amount of microbial diversity out there isn’t a bad thing. It’s a great thing. It’s wonderful, and we should promote that.

IRA FLATOW: Well, Dr. Hartmann, I want to thank you for taking time to bring us up to date on one of my favorite subjects, bacteriophages.

ERICA HARTMANN: Yeah, thank you so much.

IRA FLATOW: Dr. Erica Hartmann, Associate Professor in the Department of Civil and Environmental Engineering at Northwestern University in Evanston, Illinois.

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