Speaker 1: Great News Extraordinaries. Doctor Katrina Whites in his back. This
Speaker 1: time she's here to talk to us about biofilms. We're
Speaker 1: going to talk about biofilms that are delicious, which she
Speaker 1: shares with the rest of her neighborhood. We're going to
Speaker 1: talk about biofilms that are adorable and you can find
Speaker 1: in the ocean. And we're going to talk about biofilms
Speaker 1: that are incredibly dangerous. And we're going to talk about
Speaker 1: how Katrina is using phages to do battle with these
Speaker 1: dangerous biofilms. And if you're dealing with an incredibly dangerous biofilm,
Speaker 1: obviously Katrina is someone that you want to have in
Speaker 1: your corner. Welcome to Daniel and Kelly's Microbial Universe.
Speaker 2: Hi.
Speaker 3: I'm Daniel. I study particles and aliens.
Speaker 1: Hello, I'm Kelly Reader Smith. I study parasites and space
Speaker 1: and I love kombucha.
Speaker 3: You are just pandering, pandering, pandering, aren't you.
Speaker 1: I will pander to Katrina. I'm a big Katrina fangirl.
Speaker 3: I also like keefer And if you had something growing
Speaker 3: on your countertop, would you like lean over and give
Speaker 3: it a lick?
Speaker 1: I have a child who licks just about everything that
Speaker 1: it hasn't killed that child yet, so probably i'd be fine.
Speaker 1: I'd rather not, but I've got pretty good evidence that
Speaker 1: that it's not often lethal.
Speaker 3: Well, on today's episode, we're going to be taking an
Speaker 3: intellectual nibble of all sorts of gooey growths.
Speaker 1: And today's intellectual nibble is inspired by a wonderful question
Speaker 1: by listener Jen. Let's go ahead and listen to Jen's question.
Speaker 4: Now, Hi, Daniel and Kelly. I recently saw an Instagram
Speaker 4: post about someone who got lee Jionella from their water floster.
Speaker 4: This cod me thinking about bio films and I love
Speaker 4: a whole episode on a topic. What do you think?
Speaker 4: I don't know if there'll be any aliens, but certainly
Speaker 4: poop will be involved.
Speaker 1: And it turns out we have the perfect person that
Speaker 1: we know to talk about biofilms.
Speaker 3: Who is it, Daniel, It's Katrina.
Speaker 1: Of course, anytime we have an excuse to bring Katrina
Speaker 1: back on the show is a good day, because you.
Speaker 3: Think she's gonna side with you on all of our
Speaker 3: disagreements so you can out vote me.
Speaker 1: Just wait and see in the episode how that turns
Speaker 1: out for me. Oh, and we've got this like long
Speaker 1: running debate about who what guest has been the most
Speaker 1: common guest on the show. And I just like to
Speaker 1: clarify that I don't really think of Katrina as a guest.
Speaker 1: I think of her as somewhere between guest and co host.
Speaker 1: You know, she's not on the show all the time,
Speaker 1: but she's like, I don't closer to co host than
Speaker 1: anything else anyway. So we wanted to ask the extraordinaries
Speaker 1: what is a biofilm to get a handle on how
Speaker 1: much folks know about biofilms, and so let's go ahead
Speaker 1: and hear what they had to say.
Speaker 5: Hey, my first thoughts were like some thin layer of
Speaker 5: organic matter on top of like a body of water.
Speaker 5: Then I thought what would the weirder thing be, and
Speaker 5: then I thought like, maybe it's some way of capturing
Speaker 5: video using biotechnology.
Speaker 2: I think that a biofilm is some sort of colony
Speaker 2: of microbes or bacteria or something that creates a film,
Speaker 2: much like a plastic film that embraces and protects some
Speaker 2: organic thing.
Speaker 3: A complete guess may be a biological film that goes
Speaker 3: round or protects bacteria, microbes, something like.
Speaker 5: That biofilm is that thin, slimy membranous gluey like film
Speaker 5: material that all my free d orders were covered with
Speaker 5: when they were born.
Speaker 6: Thanks by It is a biological film that grows in
Speaker 6: water systems, so it's actually well named.
Speaker 7: It is a thin layer of organic material, usually bacteria,
Speaker 7: I believe, maybe cyanobacteria and some of the things as well,
Speaker 7: that forms over rocks, forms over sentiment surfaces, and acts
Speaker 7: often as a preservative in the fossil record.
Speaker 8: An example of a biofilm might be the gunk on
Speaker 8: your teeth if you don't brush often, or maybe a
Speaker 8: movie about Abraham Lincoln or some such.
Speaker 9: I believe that biofilm is a natural sort of layer
Speaker 9: that some organisms have that protect them from outside invasions.
Speaker 9: I guess, almost like humans have skin, like.
Speaker 8: A thin layer of biological material.
Speaker 3: Such as bacteria.
Speaker 8: Or blue green algae that forms a film on top
Speaker 8: of water. Eventually, if they become thick enough, they become
Speaker 8: what's called a matt.
Speaker 4: Biofilm That sounds kind of like something that be on
Speaker 4: the surface.
Speaker 10: Of a leak, like a algae or something.
Speaker 5: I don't know.
Speaker 10: It might be like a shall of a cellar or something.
Speaker 6: A biofilm is not a nineteen seventies documentary about childbirth
Speaker 6: at biofilm is a layer of biological material e g.
Speaker 6: Bacteria that surfaces like you have in a fish tank.
Speaker 3: Wow, these are some great answers.
Speaker 1: So our audience actually knows quite a bit about biofilms.
Speaker 1: Can I share a fun fact that one of our
Speaker 1: audience members shared with us? Yeah? Okay, so Robin wrote
Speaker 1: and said, interestingly, biofilms can be important in paleontology as
Speaker 1: they can help stabilize sediment surfaces to make trace fossils
Speaker 1: more likely to preserve. Oh wow, anyway, long story short,
Speaker 1: biofilms are important for making fossils stick around longer. Robin,
Speaker 1: that's amazing.
Speaker 3: Thank you so much for showing very cool. Yes, wow,
Speaker 3: ancient bacteria are helping preserve the fossil record.
Speaker 10: I know.
Speaker 1: So cool And so anyway, I love when when listeners
Speaker 1: are like, oh, actually I could have been a guest
Speaker 1: on your show because I know a ton of stuff.
Speaker 1: Another listener works on microscopes for visualize biofilms, and I
Speaker 1: was like, oh my gosh, you all are amazing. So anyway,
Speaker 1: people made me laugh, people taught me stuff. What a
Speaker 1: great setup for this episode.
Speaker 3: Well, these are my favorite kind of episodes. We need
Speaker 3: to discovered. There's a whole topic with like a deep
Speaker 3: well of science that you never heard anything about, and
Speaker 3: so there's a lot to learn here and it can
Speaker 3: really change your perspective on like disease and how we
Speaker 3: study it and how things work inside the body.
Speaker 1: Yes, and unsurprisingly with a topic like that, you and
Speaker 1: I had a ton of fun talking to Katrina. I
Speaker 1: maybe had even more fun because she did sign with
Speaker 1: me a lot, and so maybe we should go ahead
Speaker 1: and just jump into the episode.
Speaker 3: It's my great pleasure to once again introduce Professor Katrina Whitson.
Speaker 3: She's the most frequently requested guest on the pod. She's
Speaker 3: co director of the Whites and Research Institute and recently
Speaker 3: self appointed chair of in House Fermentation, colloquially known as
Speaker 3: Queen of Kombucha, potential poisoner of neighborhood children. Katrina, welcome
Speaker 3: back to the podcast.
Speaker 10: Wow, that is not the benign feeling that I have
Speaker 10: towards most microbes and our kombucha.
Speaker 1: It was a really mixed bag, butN intro there, Daniel.
Speaker 3: Well, you know we tell like it is on this podcast.
Speaker 3: You know, if we don't sugarcoat anything, including the fact
Speaker 3: that we may be poisoning neighborhood children.
Speaker 1: Wait, have the parents of neighborhood children been contacting y'all
Speaker 1: to get a bit of additional information about what they're
Speaker 1: in bibing at your household?
Speaker 10: I think Daniel's the only one who's worried about the
Speaker 10: safety of this kombucha.
Speaker 5: But he did ask me to make a waiver.
Speaker 3: And why is that? And why is that?
Speaker 8: So?
Speaker 10: We do now have a waiver if you drink the
Speaker 10: kombucha at our house, or like if we bring it
Speaker 10: to someone's house, because our the neighborhood kids were just
Speaker 10: enjoying it and saying it tasted like apple cider, and
Speaker 10: Daniel viewed this beautiful activity.
Speaker 5: As with suspicion.
Speaker 1: Why do they sign a waiver Because we have.
Speaker 3: This thing bubbling away in the corner of our kitchen.
Speaker 3: Who knows what's growing in there. Nobody's testing it, nobody's
Speaker 3: doing any safety protocols. Now we're just feeding it to
Speaker 3: any child who wanders into the house, sending them home.
Speaker 3: You know, who knows what happens. I don't want to
Speaker 3: be responsible.
Speaker 5: The kombucha waiver is mostly a sarcastic document.
Speaker 1: Just to be clear, I feel like I have so
Speaker 1: many questions, like how many children are wandering into your house?
Speaker 1: And do you just like leave the door open? How
Speaker 1: did this start?
Speaker 10: Oh?
Speaker 3: Man, it's one of these old fables. You know, there's
Speaker 3: a house in the forest, the children wander in. And
Speaker 3: then you know the old lady who mixed kombucha in
Speaker 3: the forest.
Speaker 5: Oh, gome back.
Speaker 3: On you, let me try that one again.
Speaker 1: Oh my gosh.
Speaker 3: And then you know the beautiful young scientist who mix
Speaker 3: kombucha in the forest, you know, draws them in with
Speaker 3: her poison.
Speaker 1: I need Daniel to survive so that we can't continue
Speaker 1: recording together. So I am cutting off this guest introduction
Speaker 1: right here. We are moving on to the meat of
Speaker 1: the interview. Katrina. We are so excited to have you back,
Speaker 1: Daniel aside, and and today we're talking about biofilms, which
Speaker 1: is another one of the many amazing things that you
Speaker 1: work on. And so let's start with what is a biofilm?
Speaker 1: And I'd like to mention since you didn't hear the intro,
Speaker 1: because we're recording this before even Daniel gets to hear
Speaker 1: what our extraordinaries had to say about biofilms. We got
Speaker 1: a lot of great answers. Our audience is excited about biofilms.
Speaker 1: So let's start there, Katrina, what is a biofilm, Well.
Speaker 10: A biofilm is a structured community of microbes that are
Speaker 10: living together in a sticky matrix that they produce themselves
Speaker 10: so that they can face the world together as opposed
Speaker 10: to facing the world alone. And so they are unicellular organisms,
Speaker 10: but they choose to live in these communities. It can
Speaker 10: be just one kind of microbes, it can be different
Speaker 10: kinds of microbes, and they live in these structured communities
Speaker 10: surrounded by a goo of their own making, and as
Speaker 10: a result, they can stick to surfaces, they can float
Speaker 10: together in clumps, and they can be protected from all
Speaker 10: kinds of evils that might change the course of their
Speaker 10: lives in the world.
Speaker 1: What a joy to live in the goo secreted by
Speaker 1: those around you.
Speaker 5: It's not for everyone.
Speaker 3: It's like a little hoa, right exactly. You live in
Speaker 3: a gated community. So this is really fascinating because it
Speaker 3: sounds like it's sort of in between the usual way
Speaker 3: we think about organisms, like either you got individual cells
Speaker 3: on their own face in the world, and all the
Speaker 3: dangers of you know, people offering them kombucha versus like
Speaker 3: multicellular organisms, you know, like lions and tigers and whatever,
Speaker 3: where every cell has its own role and they're specialized
Speaker 3: and they all work together. So this is something sort
Speaker 3: of in between. Right, there's still as you say, unicellular,
Speaker 3: which I guess means they're all basically the same, but
Speaker 3: now they're forming like a macroscopic blob, so they can
Speaker 3: work together somehow.
Speaker 5: Yeah, exactly.
Speaker 10: So, I mean it doesn't have to be that they're
Speaker 10: all the same to be in a biofilm. It can
Speaker 10: be very different types of microbs that come together to
Speaker 10: form a biofilm. But yeah, they could also be identical
Speaker 10: sister cells and they are independent cells, the same type
Speaker 10: of cell, but they all live together and they do
Speaker 10: form structured communities where that's driven by the gradients of
Speaker 10: nutrients around them.
Speaker 3: What do you mean when you say structured communities, like
Speaker 3: some guys are on the outside and some are in
Speaker 3: the inside, or what do you mean by structure?
Speaker 5: Exactly?
Speaker 10: Yeah, I mean the way that when the biofilm gets started,
Speaker 10: somebody's got to produce something sticky and then that will
Speaker 10: help the first cell.
Speaker 3: That's the way a lot of fun projects start. Yes, Oh, who's.
Speaker 1: The sticky guy in the group? Gross?
Speaker 3: All right, somebody makes something sticky. All right, walk us
Speaker 3: through a Katrina.
Speaker 5: Yeah, somebody has to make something sticky.
Speaker 10: And then either that helps the first cell stick to
Speaker 10: a surface. Then either it can multiply you know, they're
Speaker 10: sitting and replicating in the middle of all this too,
Speaker 10: or other cells can come by and stick and become
Speaker 10: part of the community, and then they have really interesting
Speaker 10: molecular communication going on. And since most bacteria live in biofilms,
Speaker 10: probably eighty percent, there's a crazy diversity of how this happens.
Speaker 10: But you know, a classic example in a textbook would
Speaker 10: show a couple of microbes sitting on a surface and
Speaker 10: then as they get bigger and denser, they start to
Speaker 10: communicate with molecules to shout out about their density, and
Speaker 10: then that helps other processes happen. You know, they're used
Speaker 10: to living in these communities, so the molecules they're able
Speaker 10: to produce have all been selected for an evolution to
Speaker 10: be able to do things in biofilms.
Speaker 1: And that communication, I think I remember is it called
Speaker 1: quorum sensing? And if it is quorum sensing? Does that
Speaker 1: mean that we get to talk about the squid? Because
Speaker 1: every chance I get, I want to talk about the squid.
Speaker 10: That is a great example. And yes, that's a perfect
Speaker 10: example of quorum sensing.
Speaker 3: What's a quorum and why do we want to sense it?
Speaker 10: A quorum is just like a count, you know, like
Speaker 10: a number of people in the room, Like do we
Speaker 10: have a quorum? Like are there enough people here that
Speaker 10: we can call it a thing? And then sensing just
Speaker 10: means that they are sensing their own quorum.
Speaker 3: I see. And how does this work on the squid?
Speaker 10: Well, the squid is such a cool example. So there
Speaker 10: are these beautiful bobtail squid that the whole system was
Speaker 10: discovered in. And this was discovered by Margaret McFall nye
Speaker 10: who's now up at Caltech and her husband, Ned Ruby,
Speaker 10: who's a microbiologist. The two of them together have been
Speaker 10: working on this for decades and it's really it'll blow
Speaker 10: your mind.
Speaker 3: Are they like a little mini science biofilm?
Speaker 10: Well, you know what, they actually created a science biofilm
Speaker 10: because every person they trained fell in love with the
Speaker 10: squid and went off in the world to start their
Speaker 10: own lab to study the squid. And now there's these
Speaker 10: photographs of the sixty or one hundred labs that are
Speaker 10: all working on squid Vibrio the microbe that causes this
Speaker 10: phenomenon around the world.
Speaker 5: So that is actually a good way to look at it.
Speaker 1: But now I'm wondering who the sticky guy is out
Speaker 1: of that group. But let's move on. We don't need
Speaker 1: to know who the sticky guy is, all right, let's
Speaker 1: talk about the amazing squid and their amazing microbes.
Speaker 10: Yeah, well, these squid have evolved a relationship with a
Speaker 10: microbe called vibrio. Just as a big picture level, the
Speaker 10: Vibrio inhabit a light organ that the squid have, and
Speaker 10: when this vibrio, the bacteria and this light organ get
Speaker 10: dense enough, they quorum sense and actually produce light. Wow,
Speaker 10: and that light in the light organ will help the
Speaker 10: squid by canceling out their own shadows, and so then
Speaker 10: they're safer in the world because prendors can't detect them
Speaker 10: as easily because they don't have a shadow.
Speaker 3: Wait, so there's a squid floating around and it's casting
Speaker 3: a shadow because there's a source of light behind it.
Speaker 3: But then the bacteria in the squid produce the light
Speaker 3: to cancel out that squid shadow exactly.
Speaker 5: Wow, So that's the big picture thing going on. But
Speaker 5: there's a real biofilm story here.
Speaker 10: And so basically, when a squid is born, in the
Speaker 10: first six hours of its life, a single vibrio has
Speaker 10: to get into its light organ and this is this happens.
Speaker 10: I mean, there's tons of fibrio bacteria floating in the ocean,
Speaker 10: so the chances are very good that it'll work.
Speaker 5: But wherever squid live, this works.
Speaker 10: That a vibrio cell that gets into the light organ
Speaker 10: and starts multiplying, and this is.
Speaker 5: Critical for its survival.
Speaker 10: So it's like really interesting to think about the co
Speaker 10: evolution of the squid always needing to be in a
Speaker 10: place where there's a vibrio that can get in there
Speaker 10: in the first six hours.
Speaker 3: Why does it have to be in the first six hours.
Speaker 10: That's a really good question that Margaret McFall and I
Speaker 10: has answered in front of me multiple times.
Speaker 5: So let's see if I can come up with a
Speaker 5: good answer.
Speaker 10: But I mean, it's it's early enough in the squid's
Speaker 10: life that the vibrio gets in there, and I think
Speaker 10: that the light organ won't develop properly without the vibrio
Speaker 10: being in there. But I don't know, doctor McFaul, and
Speaker 10: I can answer that question for real, So, yeah, you
Speaker 10: need the vibrio in there, and it's it starts multiplying.
Speaker 10: And I don't know what age this daily cycle begins,
Speaker 10: but I think it's pretty early on that the vibrio
Speaker 10: will copy make copies of themselves inside the light organ,
Speaker 10: and once they hit a certain density a quorum, then
Speaker 10: the vibrio are capable of communicating within themselves to produce
Speaker 10: this smalllecule which causes light. And then every morning, the
Speaker 10: light organ ejects ninety five percent of the bacteria and
Speaker 10: the cycle starts all over again.
Speaker 5: So then they build up the density.
Speaker 10: Of microbes and it's actually at night that they are
Speaker 10: dense enough to do this light producing phenomenon with the
Speaker 10: quorum sensing. And that always confuses me because I think
Speaker 10: of the shadow as being more important during the day,
Speaker 10: but these squid are nocturnal and it's actually the shadow
Speaker 10: of the moon that's being canceled out by the light organ.
Speaker 1: It is such a cool system.
Speaker 5: It is. It's amazing.
Speaker 3: So the bacteria don't know if it's day or night.
Speaker 3: They're just producing light, but the squid's light organ ejects
Speaker 3: them when it doesn't want light, and then they grow
Speaker 3: back when it needs light again exactly.
Speaker 10: So it's timed so that they eject them in the morning,
Speaker 10: then the density is low again. Then they have all
Speaker 10: day to build that density back up, and at night
Speaker 10: there's enough of them to do the quorum sensing and
Speaker 10: produce light.
Speaker 5: And I think it's also.
Speaker 10: Because you need a fresh crop of healthy, young bacteria
Speaker 10: to be making light. I think if you left them
Speaker 10: in there for too long, they wouldn't really be in
Speaker 10: good shape for that job anymore.
Speaker 1: And presumably the bacteria need to get back out into
Speaker 1: the environment if they can hope to infect a new
Speaker 1: light organ and keep the cycle going. And so is
Speaker 1: getting out into the environment part of I don't know
Speaker 1: the psych Does it help the bacteria in that way
Speaker 1: or is it just they get booted?
Speaker 8: Yeah.
Speaker 10: Actually, Vibrio are kind of famous for being good at
Speaker 10: living independently in water and then also inside animals, and
Speaker 10: so the probably the most famous vibrio that people on
Speaker 10: this podcast have heard of is Vibrio cholera, and cholera
Speaker 10: also can live in water and it's perfectly happy living
Speaker 10: its life without a host. But if it does come
Speaker 10: into contact with a host in the case of the diarrhea,
Speaker 10: we've all heard about the cholera syndrome. That is, when
Speaker 10: the cholera gets into the gut and has a totally
Speaker 10: different lifestyle. Similarly, the vibrio and the squid can live
Speaker 10: independently in the ocean, or they can go into the
Speaker 10: light organ.
Speaker 1: Okay, cool. So it's got like this safe little home
Speaker 1: that it can reproduce inside of, and then every morning,
Speaker 1: after it's made a load of babies, it just releases
Speaker 1: the bacteria babies out into the world and then it
Speaker 1: gets to start the cycle again.
Speaker 5: Exactly cool.
Speaker 1: So it benefits from the squid not getting eaten too,
Speaker 1: because it gets to make babies every day.
Speaker 5: Yeah yeah, like a.
Speaker 10: Little protected zone to live in for a day.
Speaker 5: Exactly yeah.
Speaker 3: And why does it have to be a biofilm? Why
Speaker 3: can't it just be like a bunch of these guys
Speaker 3: floating around inside the light organ.
Speaker 10: I think we talk about that particular system as a
Speaker 10: biofilm because of the communication going on that they have
Speaker 10: to be at a certain density for that communication to work.
Speaker 10: So I guess that's kind of a circular definition. But
Speaker 10: I mean basically, you're not going to get light if
Speaker 10: they aren't at a density that allows them to communicate, like, hey,
Speaker 10: we're all here.
Speaker 5: And that's when they decide to produce the light.
Speaker 10: So that definition has to do with density, and they're
Speaker 10: all living inside that light organ, so they're corralled together.
Speaker 10: In other cases, the biofilm forms even without any kind
Speaker 10: of physical sac that they're living in, like this light organ.
Speaker 10: So biofilms can form in all different kinds of environments.
Speaker 10: They can be more out in the wild and just
Speaker 10: decide to clump together too, I see.
Speaker 3: So it's like the collective action here. That's crucial. Yeah,
Speaker 3: And I think the question in my mind was, you know,
Speaker 3: why would these vibria make light? But the answer is
Speaker 3: then they're useful for the squid and it's a co evolution. Right,
Speaker 3: They've done this thing which for themselves is irrelevant, but
Speaker 3: it's helpful for their host and it's good for them
Speaker 3: if their host lives.
Speaker 5: That's pretty incredible, Yeah, it really is. It's amazing.
Speaker 3: Right.
Speaker 1: So we've talked about the most delicious biofilm, which is kombucha.
Speaker 1: We've talked about at your own risk. I take that.
Speaker 1: I love that risk. It's a delicious risk.
Speaker 3: We are not endorsing kombucha on this podcast.
Speaker 1: By the way, Well we are.
Speaker 10: Oh that might not be a joint decision.
Speaker 1: Hands up, who's endorsing kombucha?
Speaker 2: Wait?
Speaker 3: No, no procedural election. Oh my god. Okay, the podcast
Speaker 3: has gone down in flames. You know, we used to
Speaker 3: be that podcast that didn't just like push supplements and
Speaker 3: you know, unstudied at home brewed randomness, you know, but hey,
Speaker 3: now that's who we are.
Speaker 4: You know.
Speaker 10: Well, my objection to supplements does not include kombucha.
Speaker 5: Kombucha is the.
Speaker 10: Epitome of like non processed. You know, there's no I'm
Speaker 10: not making any claims. I'm not saying you should like
Speaker 10: put kombucha to cure all your ills. I'm just saying
Speaker 10: it's delicious.
Speaker 1: Yeah, right, And Daniel, you're like anti white chocolate without
Speaker 1: any science. So I feel like Katrina and I get
Speaker 1: to be pro kombucha just because it's delicious.
Speaker 3: Well, when we all go to prison, you know, I
Speaker 3: guess you guys will enjoy the you know, toilet brewed
Speaker 3: pruno or whatever they make. There are the equivalent what.
Speaker 1: What's totally different. Totally different. Really, we're moving on. We've
Speaker 1: talked about the most delicious biofilm. We've talked about what
Speaker 1: I consider it to be the cutest biofilm, which is
Speaker 1: the biofilm that makes the squids light up, very cute,
Speaker 1: and now let's talk about a not so lovely kind
Speaker 1: of gross biofilm. So Jen the listener shared the story
Speaker 1: about Legionella in the water flosser, Can you tell us
Speaker 1: a bit about what was happening there and why this
Speaker 1: is a dangerous biofilm?
Speaker 5: Yeah, for sure.
Speaker 10: So you know, a lot of the bacteria that you
Speaker 10: find living in water, Gram negative bacteria are good at
Speaker 10: forming biofilms. Now, I don't want you guys to leave
Speaker 10: thinking that this is always.
Speaker 5: A bad thing.
Speaker 10: I mean, our wastewater treatment plants entirely depend on biofilms
Speaker 10: often formed out of these kind of Gram negative bacteria,
Speaker 10: and that is purifying our water. So you know, it's
Speaker 10: not necessarily bad that we have some bacteria in our water.
Speaker 10: But even after wastewater treatment processes conclude, there are usually
Speaker 10: a few bacteria left in the water. So in your
Speaker 10: tap water, there's some bacteria. In fact, in bottled water,
Speaker 10: there might be even a little more bacteria because they
Speaker 10: have time to grow in there, and those are often
Speaker 10: Gram negatives that could cause disease if the right circumstances emerge. Now,
Speaker 10: when you're using a water flosser, there is a chance
Speaker 10: for some water to be kind of sitting around for
Speaker 10: a while.
Speaker 5: Anytime there's water sitting.
Speaker 10: Around like that, there's a chance that the density of
Speaker 10: the bacteria will increase.
Speaker 5: And if especially if.
Speaker 10: You're immune compromised, but you know wrong place at the
Speaker 10: wrong time, the bacteria that are.
Speaker 5: Sitting in standing water can cause trouble.
Speaker 10: And in fact, after the pandemic, all those office buildings
Speaker 10: that had water sitting in pipes that never got run,
Speaker 10: they often actually had pretty high densities of the bacteria
Speaker 10: that caused the trouble in this water floster Legionella. Legionella
Speaker 10: is just a type of GRAM negative bacteria. But I
Speaker 10: know that there is an issue with the water in
Speaker 10: the buildings after the pandemic, and there were these protocols
Speaker 10: that you had to run the water for a long
Speaker 10: time and try to get rid of this legionella so
Speaker 10: it didn't cause trouble. So that's exactly what happened in
Speaker 10: this water flosser incident. The reason they you have to
Speaker 10: watch out for letting standing water sit in a water
Speaker 10: floss is that those Legionella can grow up to high
Speaker 10: enough densities to cause trouble. And so you know, if
Speaker 10: you get a big dose of Legionella, that is not
Speaker 10: a good thing.
Speaker 1: Well let's take a break and when we get back,
Speaker 1: we're going to talk about why big doses of Legionella
Speaker 1: are not a good thing. And we're back, and we
Speaker 1: just heard a story about a water floss that was
Speaker 1: contaminated with biofilms of Legionella. And Katrina was telling us
Speaker 1: that that is bad. Yes, why is that bad?
Speaker 5: Well, it's not always bad.
Speaker 10: I mean we're often exposed to bacteria, but a higher
Speaker 10: density of Legionella can be aerosolized and get into the
Speaker 10: lungs and that can cause a kind of pneumonia. It's
Speaker 10: called Legionnaire's disease. So water flossers can lead to aerosolization
Speaker 10: of the bacteria and then if you breathe those in
Speaker 10: that can cause trouble. So really the message here is
Speaker 10: put some fresh water or like rinser water floster out
Speaker 10: with some vinegar so that you don't get a bunch
Speaker 10: of bacteria living in there.
Speaker 3: And what's the biofilm connection. I can imagine standing water
Speaker 3: bacteria growing. That's bad, But do these guys form a
Speaker 3: biofilm and that makes them extra dangerous or what's the situation?
Speaker 10: Yeah, they just they The way they face the world
Speaker 10: is they clump up and they form a sticky biofilm
Speaker 10: inside the water floster.
Speaker 5: That's their main motive of living.
Speaker 10: And so those they just they do form biofilms inside
Speaker 10: the water floster, and that allows them to grow into
Speaker 10: higher densities. I Mean, the thing that just blows my
Speaker 10: mind is that microbs can live in tap water. I
Speaker 10: think of that as a pretty nutrient poor environment, Like,
Speaker 10: isn't that amazing that there's enough going on in there
Speaker 10: that the bacteria can eke out an existence. But part
Speaker 10: of how they pull that off is that they share.
Speaker 10: So they live in these sticky biofilms and they share
Speaker 10: nutrients and that's part of how they can survive. And
Speaker 10: they're growing really slowly. I mean, that's a big part
Speaker 10: of the trick of surviving out in the world.
Speaker 5: For most microbes. They're not replicating quickly. Their metabolisms are.
Speaker 10: Like super super slow, but if you leave them for
Speaker 10: long enough, they'll grow up to a point that they
Speaker 10: could cause trouble.
Speaker 3: Could you say more about what it means to be sharing.
Speaker 3: I mean, I understand that they're in the same biofilm
Speaker 3: and so they sort of have a common purpose. But
Speaker 3: are they like passing nutrients to each other? Are they
Speaker 3: talking to each other you mentioned earlier, you know there's
Speaker 3: some chemical signaling. Is this a social community that's like
Speaker 3: helping each other out?
Speaker 5: I mean to call them social and helping each other out.
Speaker 10: Could be accused of being anthropomorphizing the bacteria, but I
Speaker 10: think that's a reasonable way to look at it.
Speaker 5: I mean, yes, they are living in.
Speaker 10: This goo that's a it's got a liquid component to it,
Speaker 10: so they can pass soluble nutrients around to each other.
Speaker 10: So they're averaging out their acquisition of nutrients by sharing
Speaker 10: them throughout the community. So in this field, there's even
Speaker 10: interesting examples of what people call cheating, where one microbe produces,
Speaker 10: say a useful enzyme that can go and break down
Speaker 10: fibers into sugars that are able to feed the cells directly.
Speaker 10: But some of the microbes might decide not to produce
Speaker 10: those enzymes, and they still benefit from getting the nutrients
Speaker 10: that the other microbes helped them acquire by producing those enzymes,
Speaker 10: and so then they're called cheaters.
Speaker 5: So yeah, there's all.
Speaker 10: Kinds of social dynamics that people study inside biofilms. And yeah,
Speaker 10: imagine you're living in a water flosser with some tap
Speaker 10: water coming by, and there's the occasional molecule of iron
Speaker 10: or something useful that pops up, and if that molecule
Speaker 10: of iron lands in the biofilm, the energy that can
Speaker 10: be acquired from using that iron is averaged out across
Speaker 10: cells as opposed to just helping one cell at a time.
Speaker 1: Is there a way to punish the cheaters? Like, do
Speaker 1: the bacteria have ways of enforcing compliance? Multicellular animals have
Speaker 1: punishment methods for going after cheaters?
Speaker 10: Yeah, what a cool question. I really think that's a
Speaker 10: science question. I know people study that, but my understanding
Speaker 10: is that it's pretty hard to punish the cheaters inside
Speaker 10: a biofilm, but it's still worth it for the other
Speaker 10: cells to produce those enzymes because they need them themselves
Speaker 10: as well.
Speaker 5: So there's really.
Speaker 10: Interesting dynamics there, and evolutionary biologists who are studying whether
Speaker 10: or not there are selection mechanisms like that, but I
Speaker 10: personally don't know about them.
Speaker 3: But the social analogy makes me think that the right
Speaker 3: way to think about this is not as a bunch
Speaker 3: of cells that are sort of approximating a multicellular organism,
Speaker 3: but more like a bunch of cells building a little
Speaker 3: society the way multicellular organisms do, right, like humans live
Speaker 3: in little groups that help each other out and average
Speaker 3: over the food and share tasks. Is that a fair
Speaker 3: way to think about a bunch of bacteria sort of
Speaker 3: living together.
Speaker 5: Yes, I think so.
Speaker 10: But they also don't have as much capacity for specialization.
Speaker 10: I mean, our bone cells and our blood cells are
Speaker 10: extremely different, and it really blows my mind that there's
Speaker 10: the same DNA underneath those two cell types, right. They
Speaker 10: just you can't imagine them being more different bacteria, don't.
Speaker 10: They have some differences in physiology and structure in different
Speaker 10: parts of a biofilm, but they're not that different in
Speaker 10: my opinion. I mean, maybe there's a listener out there
Speaker 10: who has a counter example, which I would love to hear,
Speaker 10: but I have a really cool example. When you're ready
Speaker 10: about the structures that biofilms form in the face of
Speaker 10: nutrients that they need.
Speaker 1: I was born ready, let's go yeah, honest.
Speaker 10: So there's this one kind of bacteria, pseudomonous that you've
Speaker 10: probably heard of it. It can cause infections. It's a
Speaker 10: gram negative bacteria lives in our tap water, and it's
Speaker 10: really good at forming biofilms. Now, the thing about the biofilm,
Speaker 10: you might think of it as just a uniform glop,
Speaker 10: but the problem is each cell in that biofilm needs
Speaker 10: oxygen and other nutrients to be able to run their metabolism.
Speaker 10: And so actually pseudomonous has these really cool molecules that
Speaker 10: initially got described as toxic virulence factors. They're literally being
Speaker 10: identified because of their capacity to cause disease virulence factors.
Speaker 10: But from the perspective of the pseudomonis that's not what
Speaker 10: they're doing at all. These molecules are critical to the.
Speaker 5: Energy flow in the biofilm.
Speaker 10: And so it turns out when you let us pseudomonous
Speaker 10: culture grow for a while, it kind of turns bluish green.
Speaker 10: You might have even seen it before, like, I don't know,
Speaker 10: actually the places you would have seen it are. I
Speaker 10: see it in my lab all the time, or like
Speaker 10: a gross toe infection or something, but that's hopefully not.
Speaker 5: Something anybody seen.
Speaker 10: But anyway, they turn this bluish green from these beautiful
Speaker 10: molecules that are sometimes thought of as virulence factors, but
Speaker 10: in reality, the reason the pseudomonis cares having these molecules
Speaker 10: is because they help with the energy flow in their biofilms.
Speaker 10: So the cells that can't get to the surface to
Speaker 10: get the oxygen instead have access to these molecules that
Speaker 10: I sometimes call snorkels because they basically are like transfer
Speaker 10: they're like transferring the same function that the oxygen would
Speaker 10: be playing in the community. That same function can be
Speaker 10: performed by these green.
Speaker 5: Molecules blue and green molecules.
Speaker 10: They're called phenazines, and they can act as electron acceptors,
Speaker 10: so they're like alternatives to oxygen in the energy flow
Speaker 10: for the biofilm. And so the amazing thing that I've
Speaker 10: seen this is also from Caltech, Diane Newman's lab at Caltech.
Speaker 10: They'll make mutant pseudomonous where they take away the capacity
Speaker 10: to make these molecules, the colorful so called virulence factors,
Speaker 10: and when you try to grow pseudomonous biofilm without those
Speaker 10: virulence factors, it forms these beautiful structures that increase the
Speaker 10: surface area. And so instead of having just like a
Speaker 10: smooth top, they have all these like invaginations so that
Speaker 10: the surface area is expanded. And so the only way
Speaker 10: the biofilm could come up with to like breathe without
Speaker 10: the help of these molecules to act as snorkels, was
Speaker 10: to form all these extra structures that expand the surface
Speaker 10: area so that each cell is closer to some oxygen.
Speaker 3: So these guys really are more sophisticated than just like
Speaker 3: a glop of cells. They have like infrastructure that lets
Speaker 3: the cells in the middle that can't access the oxygen
Speaker 3: still breathe. And if you're saying, if you take that
Speaker 3: infrastructure away, then they all basically push to the surface
Speaker 3: and make all these ripples exactly.
Speaker 10: Yeah, I think that's so such a beautiful example. And yeah,
Speaker 10: google a fenazine mutant of pseudamonis and you will see
Speaker 10: this beautiful structure.
Speaker 5: They're very cool looking.
Speaker 1: You know, the other day, Daniel said, Google raccoon eats
Speaker 1: baby's face, And I gotta say, I really prefer I said,
Speaker 1: don't I really prefer Katrine's Google search suggestions to Daniel's
Speaker 1: Google search suggestions.
Speaker 3: You're just drinking the kombucha over there, Kelly.
Speaker 1: I'm glugging the kombucha. Give me more.
Speaker 10: I mean, drinking kombucha means you avoid alcohol, but you
Speaker 10: still get to have a sophisticated you know, tearir of fermentation,
Speaker 10: any goodness that otherwise you might get.
Speaker 1: From your wine. Heels just such a like fun killer,
Speaker 1: isn't he? That's what I think.
Speaker 3: Staying alive, staying alive overrated anyway.
Speaker 10: Daniel will eat cheese, yogurt, He'll drink beer, he'll drink wine.
Speaker 5: I do not understand the line.
Speaker 1: It's it's arbitrary, seems arbitrary to me.
Speaker 3: I will not eat homemade cheese. I'm sorry, no homegrown funk.
Speaker 1: I hate to feel like I'm giving Daniel a win
Speaker 1: here by transitioning us to conversations about disease. But should
Speaker 1: we talk a bit more about disease? So what I'm
Speaker 1: wondering is like, say you were going to get infected
Speaker 1: by a million pathogenic bacteria, would you rather get infected
Speaker 1: by a million pathogenic bacteria that are individuals or a
Speaker 1: million pathogenic bacteria that are part of a biofilm, which
Speaker 1: would likely be worse for you to get infected by.
Speaker 5: Wow, that's a really cool question.
Speaker 10: I mean, overall, biofilms are the hardest to get rid of,
Speaker 10: so I think I would probably prefer not to have
Speaker 10: the biofilm. But I mean then i'd wanted little more
Speaker 10: rules on what the non biofilm bacteria or microbes could be,
Speaker 10: because I mean, I wouldn't want to get infected by
Speaker 10: like ebola viruses.
Speaker 5: They'll just take you down so quick, So I think
Speaker 5: i'd prefer You know, the biofilm is going to be.
Speaker 10: A slow disaster, Okay, so I guess it depends on
Speaker 10: the timescale.
Speaker 1: Do viruses make biofilm?
Speaker 5: Oh? What a cool question. I don't know, I mean,
Speaker 5: not tech.
Speaker 10: The definition of a biofilm kind of requires cells, and
Speaker 10: viruses are not cells. But do viruses ever kind of
Speaker 10: like clump up together and help each other? And I
Speaker 10: think that can happen. Actually, So that's a cool question.
Speaker 3: But what is it that makes a biofilm harder for
Speaker 3: our immune system to protect us against?
Speaker 5: Great question?
Speaker 10: So, I mean when a biofilm forms one of these structures,
Speaker 10: then imagine you're trying to get antibiotic drugs into that,
Speaker 10: or imagine you're an immune cell trying to get rid
Speaker 10: of that. You know, they're bigger and they're they're able
Speaker 10: to hide out, So it's much harder to get rid
Speaker 10: of every last cell in a biofilm because they have
Speaker 10: more structure and density that makes it harder to reach.
Speaker 10: So getting antibiotics into a biofilm is really hard.
Speaker 5: So yeah, so that's one reason.
Speaker 10: And in general, they also just grow really slowly, so
Speaker 10: it's not even only about getting antibiotics in there, it's
Speaker 10: about if the antibiotics mode of action involves stopping replication,
Speaker 10: the biofilm can just be like, yeah, well I'm not
Speaker 10: replicating until twenty years from now, so I don't really
Speaker 10: need you, know, I don't care about you. I mean,
Speaker 10: they really can be like very very slow growing in
Speaker 10: the biofilm.
Speaker 5: So those are reasons that they're hard to get rid of.
Speaker 10: So people who are to compromise for different types of reasons,
Speaker 10: like for example, if you have cystic fibrosis, which already
Speaker 10: predisposes you to having a lot of mucacy build up
Speaker 10: in your lungs, that's a perfect environment for a biofilmy
Speaker 10: bacteria to take hold, and as a result, people can
Speaker 10: have lung infections that go on for decades. You know,
Speaker 10: that's a tough situation, but I guess it's it's a
Speaker 10: slower situation than than a terrible virus could have.
Speaker 3: So it seems like it's an advantage for the bacteria
Speaker 3: to make a biofilm. Do all bacteria make biofilm? And
Speaker 3: if not, why not?
Speaker 10: The super majority of bacteria do make biofilms, But there
Speaker 10: are some bacteria that prefer to grow planktonic, like one
Speaker 10: at a time, in liquidic.
Speaker 3: Awesome word. Yeah, that's the new word for being an introvert. Hunt. No,
Speaker 3: I'm just planktonic.
Speaker 10: It's so funny that that's like a new word to you.
Speaker 10: That's really interesting. Yeah, I never thought of it that way.
Speaker 10: I like that. And then so then you know, your
Speaker 10: first instinct might be like, oh, so you mean in
Speaker 10: the ocean, the bacteria just are all by themselves planktonic
Speaker 10: in the ocean, But they're actually not. Cyanobacteria, for example,
Speaker 10: are famous for making clumpy biofilms even in the ocean.
Speaker 10: But yeah, there's some types of bacteria that tend to
Speaker 10: grow planktonically I don't actually have a good reason why.
Speaker 10: I mean, I can tell you in my own lab,
Speaker 10: if you grow shaking cultures of bacteria, they tend to
Speaker 10: grow planktonically.
Speaker 3: Then shaking cultures.
Speaker 10: Yeah, Like most of the bacteria in labs are grown
Speaker 10: in rich media, so just think of it like kombucha
Speaker 10: and then yeah, and then we put them on what
Speaker 10: we call a shaker, which shakes at three hundred rotations
Speaker 10: per minute and like really mixes things up. And that's
Speaker 10: a case where the bacteria often do not go biofilmy
Speaker 10: because they're just like a lot of the advantages of
Speaker 10: a biofilm to get nutrients and so on are removed
Speaker 10: if you're shaken around like that and you've got all
Speaker 10: the nutrients you need, they don't bother to make biofilms
Speaker 10: in that circumstance. But which tells you how our lab
Speaker 10: conditions are actually terrible for mimicking infections, which is a
Speaker 10: big topic to talk about because the overwhelming majority of
Speaker 10: microbiology and labs happens with planktonic bacteria in fast growing conditions,
Speaker 10: but the overwhelming majority of infections are in essentially low
Speaker 10: nutrient conditions. Even though that's like ironic because obviously a
Speaker 10: human is full of delicious nutrients. But if you're growing
Speaker 10: kind of in a hidden corner in a biofilm, you
Speaker 10: won't be getting that many of those nutrients. So that's
Speaker 10: a big issue, is like getting our lab cultures to
Speaker 10: do a better job of mimicking infection conditions.
Speaker 3: Do you just call humans delicious? Oh?
Speaker 10: Yes, I mean in terms of richness in useful nutrients.
Speaker 7: Yes.
Speaker 3: So when you want like neighborhood parents to trust you
Speaker 3: to send their kids over to your house to drink
Speaker 3: your kombucha, I think calling their children delicious. I'm not
Speaker 3: sure if by helping yourself out there.
Speaker 1: I think we need a special sound effect for when
Speaker 1: we've hit a dKu bingo spot on our card and
Speaker 1: cannibalism just got there, we go, there we go.
Speaker 5: That is definitely not where I was going with a right.
Speaker 1: Okay, Well, now it feels like the perfect time to
Speaker 1: take a break, and when we get back, we're going
Speaker 1: to talk a little bit more about how you study
Speaker 1: this stuff in the lab and why it involves steaks
Speaker 1: from Trader Joe's.
Speaker 3: Okay, we're back, and we're talking to Katrina about how
Speaker 3: she's working hard to be a delicious target for just
Speaker 3: the right microbes.
Speaker 5: Yes, definitely true.
Speaker 11: I mean, if you drink your kombucha and you eat
Speaker 11: your fiber, hopefully you will attract the right community of
Speaker 11: microbes to form healthy biofilms in your gut and not
Speaker 11: disease related bacteria biofilms which are less common.
Speaker 1: And if that doesn't work out, you can always get
Speaker 1: a fecal transplant. And if you want to learn more,
Speaker 1: you can listen to one of our previous interviews with Katrina.
Speaker 1: We only talk about the best stuff when we have
Speaker 1: Katrina on the show, but.
Speaker 3: I think that's an important point. We've been talking about
Speaker 3: bacteria and how biofilms make it harder for our immune system.
Speaker 3: But of course lots of bacteria are not clearly pathogens, right,
Speaker 3: they do helpful stuff, and those bacteria also make biofilms.
Speaker 3: Tell us more about how biofilms can help us out.
Speaker 10: Yeah, I mean, most bacteria are living in biofilms. So
Speaker 10: every time you've heard about a bacteria, just imagine it
Speaker 10: in a sticky community with other like minded bacteria and
Speaker 10: other microbes. So the microbes that live on our teeth,
Speaker 10: they're in biofilms. You've seen that before. In fact, that's
Speaker 10: the first microbe we ever saw as humans, when Dutch
Speaker 10: draper Antonin van lewin Hook took a clump of his
Speaker 10: own dental plaque and used the hand ground glass he
Speaker 10: had made to view.
Speaker 5: The animal cules in his teeth.
Speaker 10: And those are the same microbes we all have in
Speaker 10: our teeth, and they're definitely part of our health. Gut bacteria,
Speaker 10: many of them are forming biofilms against the mucus in
Speaker 10: our guts. And I guess maybe an example that really
Speaker 10: affects humanity. Arguably one of the more important parts of
Speaker 10: our civilization is wastewater treatment and the biofilms which are
Speaker 10: often coming from gut bacteria. Let's face it, those are
Speaker 10: formed in the wastewater treatment tan that purifier water.
Speaker 1: Thank you. Biofilms in your lab, are you studying the
Speaker 1: good biofilms? Are mostly just studying bad biofilms?
Speaker 5: Oh what a good question.
Speaker 10: I mean, we are studying good biofilms in fecal samples,
Speaker 10: but when we actually do experiments in the lab, it's
Speaker 10: often way it's more about the disease causing biofilms. Specifically
Speaker 10: the kinds of bacteria that infect people who get cystic fibrosis,
Speaker 10: and then they have these long term infections in their
Speaker 10: airways with bacteria that are really good at forming biofilms.
Speaker 10: And so we actually have clinical isolates from people with
Speaker 10: cystic fibrosis at different points in their infection and the
Speaker 10: types of biofilms they.
Speaker 5: Form change a lot.
Speaker 10: So like if you grow a pseudomonus that is from
Speaker 10: a fresh infection of somebody of a human, it will
Speaker 10: form some biofilm, but you know it'll it doesn't make
Speaker 10: all that much mucous. If you grow a late pseudomonus
Speaker 10: isolate from somebody from infection that went on for decades,
Speaker 10: it will be called mucoid, and literally after a couple
Speaker 10: of days growing on a plate in the lab, it
Speaker 10: will make piles and piles of this mucasy gunk. And
Speaker 10: that clearly is a phenotype that is helping it stay
Speaker 10: in the lung inside all of that goo.
Speaker 2: Oh man.
Speaker 5: Yeah.
Speaker 1: So to transition to a paper of yours that I'd
Speaker 1: really like to talk about today, I'm wondering why Trader
Speaker 1: Joe's hasn't reached out to fund your lab, given that
Speaker 1: you have been growing biofilms on Trader Joe's steaks. Can
Speaker 1: you tell us a bit more about that, I'm sure
Speaker 1: they're throwing Yes.
Speaker 5: I can, I would happily.
Speaker 10: So, you know, we were trying to think of ways
Speaker 10: to grow bacteria to mimic the conditions inside the human body.
Speaker 10: And that's not going to be rich nutrients shaking three
Speaker 10: hundred times per minute, which is how most experiments are
Speaker 10: happening in our field right now, And so we were
Speaker 10: just thinking of different substances that we had available to
Speaker 10: us that would mimic a human infection. I mean, there's
Speaker 10: actually a lot of people who we got ideas from,
Speaker 10: like Fria Harrison in the UK. She has been studying
Speaker 10: cystic fibrosis microch for a long time and she goes
Speaker 10: to the butcher and buys pig lungs and uses them.
Speaker 5: For her infection model.
Speaker 10: And actually when I was in Malta last week at
Speaker 10: that cystic fibrosis conference, I saw one of her collaborators
Speaker 10: presenting how they were using pig lung.
Speaker 5: As a model.
Speaker 10: We've also tried like making media that has all the
Speaker 10: stuff we think will be in a cystic fibrosis mucus plug,
Speaker 10: but the steak came up because we could do it,
Speaker 10: you know. So my student Joanne Fan literally went to
Speaker 10: Trader Joe's and we actually bought quite a bit of
Speaker 10: steak and cut it into cubes and put it in
Speaker 10: a freezer so that we would have the same batch
Speaker 10: to go back to again and again for the experiment.
Speaker 10: And then we infected the steak with it was Pseudomonos
Speaker 10: was one of the ones we were using, and then
Speaker 10: we hooked it up to some pumps that could flow
Speaker 10: media through, so that was kind of mimicking how you
Speaker 10: would nutrients arriving in an infection.
Speaker 3: This sounds like act one of a horror movie, doesn't it.
Speaker 5: Yeah, it is kind of crazy that we did this,
Speaker 5: I know. Yeah.
Speaker 10: And then we tried exposing the infection to different types
Speaker 10: of antibiotics so that we could study the response of
Speaker 10: the bacteria to antibiotics in more realistic conditions.
Speaker 5: And I remember the title of the paper had thriving
Speaker 5: under stress in it.
Speaker 3: But it never like pulled itself together into some weird
Speaker 3: monster to attack your grad.
Speaker 10: Students, I mean, not that I know about, hopefully not
Speaker 10: regular And actually Daniel, our friend alone Hawkbaum, an engineer
Speaker 10: here at ECI. He was my collaborator in that project,
Speaker 10: and we had very serious meetings weekly for years discussing
Speaker 10: how to do this, and then the results when we
Speaker 10: got them back, which is kind of funny.
Speaker 1: And about those results, did it work about the way
Speaker 1: you wanted it to? Is this now a helpful model
Speaker 1: for studying biofilm.
Speaker 5: Yeah, that's a good question.
Speaker 10: It was not easy to set up, so it's not
Speaker 10: something we've done again. To be honest, I think it
Speaker 10: would require you know, the right person and the right
Speaker 10: funding to be able to support being able to do that.
Speaker 5: So it's not our current go to.
Speaker 10: But we did have really nice results out of that paper,
Speaker 10: Like it was you know, the growth rates of the
Speaker 10: bacteria were much more realistic, and the antibiotic responses were
Speaker 10: you know, the antibiotes were less effective in that model,
Speaker 10: which is exactly what we were going for. So I
Speaker 10: would say it's a really useful model in that sense.
Speaker 10: It's just kind of hard to set up. So what
Speaker 10: we're actually doing right now is we are we like
Speaker 10: to do things higher throughput. That method is not very
Speaker 10: high throughput, So we are doing everything in ninety six
Speaker 10: well plates these days, and we're buying media. One of
Speaker 10: my colleagues in Georgia in Atlanta has started a company
Speaker 10: where he's making artificial sputum media. So we used to
Speaker 10: make our own artificial media, which has things like pig
Speaker 10: musin and egg yolks and all kinds of rich things
Speaker 10: that are trying to recreate.
Speaker 5: The environment of the lung. But the problem is there's
Speaker 5: a lot of variation batch to batch and lab to lab.
Speaker 10: So now that there's a company making that media, we
Speaker 10: can all buy that media and then when we compare
Speaker 10: results across papers, at least we know we're using the
Speaker 10: same stuff. And so that actually has worked really well.
Speaker 10: And to me, it's fascinating how we'll have a really
Speaker 10: slow growing bacteria when we're using the kind of typical media,
Speaker 10: and then we'll put it into the artificial speed and
Speaker 10: media and it'll actually grow better. So I think it
Speaker 10: is helping us recapitulate infection conditions to use that media.
Speaker 10: And then we have ninety six well plates and we
Speaker 10: have this plate reader that can hold four plates, so
Speaker 10: we have really high throughput, so we can, for example,
Speaker 10: test whether a phage can infect ninety different strains intriplicate
Speaker 10: all in one day. Using that plate reader that's got
Speaker 10: the four plate capacity.
Speaker 1: We got to phages. I was hoping we'd get to phages. Okay,
Speaker 1: so could you remind us one what phages are? And
Speaker 1: then two could you tell us you know, I've been
Speaker 1: dying to know. Like you mentioned that antibiotics not great
Speaker 1: for killing a biofilm, probably because like the bacteria hiding
Speaker 1: in the center of the biofilm, antibiotics probably don't really
Speaker 1: get to them. Yeah, but maybe a phage can sneak
Speaker 1: into the middle. So yeah, what are phages?
Speaker 2: Yeah?
Speaker 1: And are they the solution to the biofilm problem?
Speaker 10: Phages are the viruses that can infect and kill bacteria,
Speaker 10: and so we're using them as alternatives to antibiotics sometimes.
Speaker 10: So if your bacteria is resisting antibiotics, it might be
Speaker 10: susceptible to phage.
Speaker 5: So that's the idea.
Speaker 10: And so yeah, there's actually really cool reasons that phages
Speaker 10: might work better than antibiotics to attack biofilms. Some phages
Speaker 10: carry enzymes that break down the gunk that forms a biofilm, So.
Speaker 5: I mean, what a great combination.
Speaker 10: I mean imagine, you know, an antibiotic is just one molecule,
Speaker 10: and it might not really be able to get in there.
Speaker 10: But the phage is a package that contains its own
Speaker 10: cism for cutting open the biofilm, and then it can
Speaker 10: get in there. And if it can infect a cell
Speaker 10: and locally multiplied, then you're increasing the dose right where
Speaker 10: you need it. So there are bacteria, phages, viruses that
Speaker 10: specialize in infecting biofilms. I personally have tried to find
Speaker 10: those ones, like we intentionally make up the gunkiest biofilm
Speaker 10: we can and then hunt for phages that are good
Speaker 10: at breaking it down.
Speaker 5: We haven't actually had a.
Speaker 10: Lot of luck with that strategy, but I know other
Speaker 10: labs that have found phages that can break down the
Speaker 10: biofilm matrix. And yeah, that's a real reason for trying
Speaker 10: to use pages as alternatives to antibiotics.
Speaker 3: And if most bacteria make biofilms, then phages in the
Speaker 3: wild that are around because they've been succeeding against bacteria
Speaker 3: must somehow be able to attack biofilms, right.
Speaker 10: Yeah, exactly, Yeah, they've had they've been evolving for four
Speaker 10: billion years, whether or not they can infect the biofilm.
Speaker 10: I mean, part of the bacterial strategy for avoiding viruses
Speaker 10: is forming the biofilm. I mean, it is a good
Speaker 10: defense mechanism.
Speaker 3: So we're like stepping into a four billion year old
Speaker 3: arms race here.
Speaker 5: That's right.
Speaker 10: Yeah, it's like that show Neighbors, except they've had four
Speaker 10: billion years.
Speaker 3: I don't get the reference, but we don't want to
Speaker 3: talk about that show.
Speaker 1: So what other ways are folks using to try to
Speaker 1: battle biofilms or antibiotics and phages the main things we're
Speaker 1: working on right now.
Speaker 5: Oh, good question.
Speaker 10: No, there's people who have all different kinds of strategies,
Speaker 10: Like you could imagine molecular adjuvants that kind of dissolve
Speaker 10: the biofilm before the antibiotic gets there, or making combinations
Speaker 10: of antibiotics that are soluble in the context of a biofilm. Yeah,
Speaker 10: I mean there's actually a lot of different kinds of strategies.
Speaker 10: I mean there's also more physical strategies. So some of
Speaker 10: the main treatments for people with cystic fibrosis include chest
Speaker 10: compression vests or exercise with the hope of dislodging the
Speaker 10: mucus that accumulates as part of the disease so that
Speaker 10: you can cough it back up, or you know, in
Speaker 10: the context of a wound, you can clean up and
Speaker 10: to bride the wound and remove some of the biofilm.
Speaker 1: Yeah.
Speaker 10: I think there's lots of different types of strategies for
Speaker 10: trying to go after biofilms.
Speaker 3: Katrina, I remember when you were on the show talking
Speaker 3: about phage therapy. You had a patient and you were
Speaker 3: growing phages specifically for their infection, and a bunch of
Speaker 3: folks wrote in and wanted to know, how is that going?
Speaker 3: How is that patient?
Speaker 5: Oh? Thanks for asking.
Speaker 10: So it's now March twenty twenty six, and the treatment
Speaker 10: happened in July and August of twenty twenty five, so
Speaker 10: it now it's been six months, and so I was
Speaker 10: so curious how it was going to go. We need
Speaker 10: time to tell, And so far they are still doing
Speaker 10: really well. So they had ten years or maybe even
Speaker 10: twelve years of chronic fevers from sinusitis. It was a
Speaker 10: staph infection in the nose, and so they still don't
Speaker 10: have fevers. So that's a really good sign. And I
Speaker 10: met with the doctor a few weeks go and we
Speaker 10: were saying, hey, you know, we still have these approved
Speaker 10: phages sitting in our fridge. We could repeat the treatment
Speaker 10: if that would help at this time, but actually the
Speaker 10: doctor thought that they were doing fine and did not
Speaker 10: need further treatment, so that's really amazing. They also went
Speaker 10: to have an endoscopy and overall the conditions look really
Speaker 10: a lot improved. There's not big signs of inflammation. There's
Speaker 10: still healing going on from all those years of infection.
Speaker 10: So that's a biofilm for sure. I mean that was
Speaker 10: a staff biofilm in the nose, very hard to get to,
Speaker 10: and so we did daily treatment in the nasal rints
Speaker 10: with the phage for six weeks last summer.
Speaker 3: A phase that you grew in your lab specifically to
Speaker 3: target this infection.
Speaker 5: That's right.
Speaker 10: We got the isolate from the clinical micro lab. A
Speaker 10: student in our lab slogged away for months failing and
Speaker 10: then finally succeeding at finding a phage, grew up a
Speaker 10: big that of the phage, purified it in very complicated
Speaker 10: ways that we had to learn how to do, and
Speaker 10: then we had a third party testing to show that
Speaker 10: it was sterile and didn't have any toxins in it
Speaker 10: to get FDA approval to be allowed to use it.
Speaker 10: So yeah, that's really personalized medicine, that's for sure. Wow.
Speaker 3: And did this patient have to sign a waiver similar
Speaker 3: to our kombucha waiver.
Speaker 10: Oh god, they had to sign a consent form which
Speaker 10: looked nothing like our kombucha waiver because it didn't have
Speaker 10: jokes in it.
Speaker 1: It was very serious.
Speaker 3: So you're saying, people take it really seriously when somebody
Speaker 3: grows on microbial community. All right, I'm getting eye rolls.
Speaker 1: Over here, two pairs of them. All right, Well, I
Speaker 1: think that's amazing. Congratulations And we have to, of course
Speaker 1: end on Daniel's alien question.
Speaker 3: So, Katrina, when we eventually land on alien planets and
Speaker 3: describe a microbial life, do you think those microbes will
Speaker 3: be forming biofilms or will they be planktonic?
Speaker 5: Oh? I think they'll be forming biofilms. That's that's an
Speaker 5: easy one.
Speaker 3: Because it's such an obvious advantage. Yeah.
Speaker 10: I mean, if that's the overwhelming majority of the way
Speaker 10: most microbes are growing, I could imagine them banding together
Speaker 10: and sharing nutrients.
Speaker 1: You know.
Speaker 10: I would imagine the conditions would somehow be like, really tough,
Speaker 10: but from the perspective of the microbes, they might be great.
Speaker 5: So I don't know.
Speaker 3: And when the alien citizens of that planet offer you
Speaker 3: their locally brewed confection. Are you drinking it down? Are
Speaker 3: you signing the alien waiver?
Speaker 8: Oh?
Speaker 10: Man, you mean i'd be the first person to drink
Speaker 10: alien kombuja.
Speaker 3: Yeah, she's thinking hard here, folks.
Speaker 1: Ooh, she says, yes, all right, sure, I'd do it.
Speaker 10: I mean, I wouldn't mind, like you know, i'd think
Speaker 10: of maybe I wouldn't mind a little time to test
Speaker 10: it out in other ways before I drank it.
Speaker 6: You know.
Speaker 5: But kombucha is ancient in human culture, and think of
Speaker 5: all of the people who have survived and thrived while
Speaker 5: drinking kombucha through this, not just the centuries, but the millennia.
Speaker 3: So is kombucha the most delicious form of biofilm?
Speaker 5: I think so? Yeah.
Speaker 10: So the kombucha has this disc floating on top of
Speaker 10: it called a scobie, which is the symbiotic culture of
Speaker 10: bacteria and yeast, and it's actually pulling the sugar out
Speaker 10: of the sweet tea you put in there to form
Speaker 10: this like cellulose mat at the top. And so it
Speaker 10: really is a biofham that's very visible. And I know
Speaker 10: to some people it might come across a bit disconcerting,
Speaker 10: but that's not how I view it. I'm like, man,
Speaker 10: that's so cool, you know, And like all you added
Speaker 10: was sugar and tea and it makes this thing that
Speaker 10: has all these fruity flavors in it.
Speaker 5: I think that's so amazing. Like when we shared it
Speaker 5: with a bunch of friends on Saturday.
Speaker 10: They were like, what fruit did you add? Well, I
Speaker 10: didn't add fruit. I just let the Scobie do its work,
Speaker 10: you know, And so.
Speaker 5: Yeah, I don't remember your question anymore.
Speaker 3: Say, and there you have it, folks, Katrina is pushing
Speaker 3: the bit.
Speaker 1: And I'm pushing right behind her. Well, thank you so
Speaker 1: much for being on the show, Katrina. As always, we
Speaker 1: had an absolute blast and we can't wait to have
Speaker 1: you on to talk about some other aspect of what
Speaker 1: you do in the not too distant future.
Speaker 10: Well, thank you very much for the opportunity to promote
Speaker 10: the microbes.
Speaker 5: They rule the world anyway, so might as well talk
Speaker 5: about it.
Speaker 1: Always, happy to have you here, and thank you for
Speaker 1: your patience with Daniel.
Speaker 10: I did actually really need to exercise my patience in
Speaker 10: today's episode.
Speaker 1: I'm gonna stop recording. Bye everyone, until next time.
Speaker 3: Bye, Thanks everybody for listening. Please go and do us
Speaker 3: a favor and rate the show on whatever podcast app
Speaker 3: you're using. It really helps people find us.
Speaker 1: Daniel and Kelly's Extraordinary Universe is edited by the amazing
Speaker 1: Matt Kesselman.
Speaker 3: He really is a wizard. You can also find us
Speaker 3: online on Blue Sky, Instagram, and x D and K Universe.
Speaker 3: Come engage with us.
Speaker 1: You can email us at questions at Danielankelly dot org.
Speaker 1: We really do want to hear from you, and.
Speaker 3: You can find our website www dot danieland Kelly dot org,
Speaker 3: where you'll also find an invitation to join our discord
Speaker 3: where everybody comes and talks about the amazing universe.
Speaker 1: And we also have the most amazing moderators. This is
Speaker 1: an iHeart podcast. Thanks for joining us.