Forget Going Viral - Bacterial Communication is Awesome

They they make cheese possible kind of. They help us digesting. Yeah, they make us real sick sometimes that's the best. It's very important. Well yeah, sure, yes, we've talked about before about how bacteria actually make up more of us than we do. What by cell count mass? Yeah, I think by mass it's a thing like four pounds. It's it's

not all that much. But yeah, we came across this really interesting article in Scientific American about bacteria, and even though we've kind of sort of talked about it a little bit in the past, I really wanted to do another episode about it because bacteria can talk to each

other and that's so cool. But Before we get to that, let's do a quick overview on just what bacteria are and why, other than the pure scientific inquiry into how bacteria communicate, like how that would practically affect us, right, right, So first off, I mean this is going to be a review on like elementary science level, but it's important to build the foundation. Bacteria are very small organisms. Um wait,

wait a second, yes, what do you mean small? So when we call say, Matt Frederick a bacterium, we're not meaning that literally because he's he's actually the size of many bacteria. How many more than four? Uh so at least three dozen? We're talking about usually a single cell organism, right, That's typically what bacteria are. Um. They lack though exactly

that fact is going to become interestingly complicated. They lack chlorophyll because if they had chlorophyll, then they would be probably more along the lines of the plant kingdom than of their own. They actually belong to a kingdom called prokaryota, and that is they are they are not the only inhabitants of that kingdom. Um Way, they lack a nucleus, which is what puts them there. They're prokaryotic. That means that they do not have a nucleus or other membrane

bound organelles inside of them cell command center. Yeah. Yeah, they're just sell soup inside kind of sort of. Yeah, it's not like you know, the or the cells that we are in us. They're you karyotic. They have a nucleus and membrane bound organelles and things like that. The other organism that within that kingdom is our chea. Those are the other prokaryotic organisms. So their DNA is just contained within the cell itself. There's no nucleus there to

hold it, unlike ours. It's a circular chain of DNA molecules that inhabit the bacteria or bacteria um because that's the singular, right. How Come every time I searched for stock images of bacteria, they're like a few kinds. They're they're like the hot dog bacteria, and the cheese puff bacteria, and the and then I think some spiral gigs. Spiral gigs I always think of like Arby's curly fries. Yeah, yes, it's because it's delicious bacteria. But I like my bacteria

covered in melted cheese sauce. Uh yeah, that's because the bacteria do come in and generally in three general three shapes, right, you've got the spherical ones, you've got the rod shaped bacteria, and then you have the spiral the spiro keet bacteria, which always makes me think of The Simpsons because there's the part where uh, Lisa's teacher explains that she has lyme disease and then Ralph Wiggam draws a spiro keat for her and in her get well, card I drew

you was spiro keat. You didn't see that season? No, no, no, that was the one where Lisa develops a crush on the replacement teacher who comes in because he's he's very smooth talking and doesn't talk down to the students, and she just falls in love with him. Uh. We usually use the word bacteria rather than bacteria um because we tend to talk about a whole mess of them. It's very rare that you're going to talk about a single

bacterium because steria rarely get lonely. No, they usually they usually got a group of friends together, and if they don't have a big group of friends together, they work really hard to change that. Yeah. So that's those Those are your general like simple foundational facts. About bacteria, and like Lauren was saying, there are tons of different kinds. Even within these three main classifications of shapes, there are

tons of different kinds. Some of them are beneficial to us, some of them can make you very very ill, and some of them we just don't really react, like there's no interaction, and some are pretty neutral. Yeah. Yeah, it's kind of like a you know, a D and D campaign. Really, you've got some, You've got some that are like lawful good, and then you get kaolic evil, and then true neutral.

So those are your basic types. Uh. And then we got to get on over to the how how bacteria, like the unwanted kind, the stuff we don't want in our systems, how those can interact with us and make us not feel so great. And that's one of the primary reasons why we are interested as a human population, not the three of us in this room, in studying bacteria, because of aously, people getting sick is bad. We want that to happen less often. Uh, And instead it seems

to be happening more often. And our primary means of fighting bacteria tends to be using the use of antibiotics. But we're kind of in an arms race, aren't we. Yeah, that's a great way of putting it is. It's that we come up with an antibiotic, and then bacteria can sometimes find a means to resist that antibiotic, thus making

it less effective. Any population of bacteria that still remain after an antibiotic has been moved through a system are more capable of resisting it in the future, thus creating kind of super bacteria. Yeah, it's evolution on the micro scale. And in this way, bacteria are kind of like the borg. I mean, what happens when you use a weapon on the borg? They immediately recognize that attack. Once if the attack is successful, they recognize it, they adjust their shields

so that now it absorbs it. That's why you always have to vary the frequency, right, except in antibiotics, we can't really vary the frequency. And we talked a lot about this, well, not about borgs, but about this general topic in our episode the antibiotic Dilemma, which came out

in March. But right, you know, antibiotics, the point of them is to slow down the growth of bacteria, you know, either kill them or slow them down to the point that your immune system can successfully fight off an infection. On its own. And the problem here is is that bacteria again have a lot of friends hanging out with them. They multiply so fast and so densely that colonies can

evolve to be resistant really really quickly. They divide by fission, and they can do that within twelve hours, so within the twenty four hour period the population can increase significantly. Yeah, and like you guys were saying, it's hard for antibiotics to keep up with them because the mechanisms through which antibiotics kill bacteria tend to be really easily foiled by evolution.

For example, lots of antibiotics kill by basically just stabbing bacteria in their outer cell walls, uh, kind of sort of just making them rupture all of their cell guts spill out dead bacteria. But you know, critters with stronger cell walls will survive and multiply, and future generations will

be less likely to be harmed by stabbing. So this is particularly an issue because we have become so dependent on antibiotics to solve bacterial disease problems, like we use them as blanket measures, and even healthy animals that we wind up eating we prescribe them for sometimes non relevant diseases or in cases that won't really significantly help the patient.

We use them as blanket measures in like our hand soaps and dish soaps, instead of just promoting say, food handling and regular old handwashing, which are usually just as effective. And this would be I mean, this gets exacerbated if there's a misdiagnosis. Obviously, if you were prescribed antibiotics for something that ended up being a viral infection, it's not going to help you at all. Viral infections are different

from bacterial infections. Yeah, so this is like if in a universe populated by borg we used our best weapon against the borg too, I don't know, clean the outside of our starships and then yeah, oh accidentally went past a board foot. Now they know how to stop it. That would that would be foolish of us. But yet that's maybe that was a horrible analogy. I don't know. That's kind of what we do occasionally with you know. It's it's not that people are uh, you know, kind

of doing a blanket carpet bombing with antibiotics. It's just that that it has been such an effective tool and has saved so many lives that the the desire to go to that early is very strong, oh Sharon. And before we realized that that these antibiotic resistant strains were starting to develop, it seemed like a really great plan. And but then all of a sudden we wound up with stuff like um m R s A, which I could never pronounce the full name of. I'm not even

gonna try. The cyllin resistant staff willocaucus arius. Yeah, go Joe, right, that sounds good to me. Methicillin resistant staff lacaucus arius. Well there we go, now, you know, and knowing's half the battle. The other half is red lacing. The other way you could say is that it's staff. It's a staff infection that has become resistant to the antibiotic methyicillin. Yes, because normally staff infections are just skin infections, but in hospitals, m R. S A can cause deadly blood and surgical

infections and pneumonia, nasty stuff like that. It's this is also where we got stuff like gnarrhea that never goes away. Yeah, bad times. So okay, we still need to use antibiotics

in some situations. They still save lots and lots of lives unless we can find some other way of fighting bacteria, and that leads us into a discussion about how bacteria act on moss, because there's a there's a question that you have to ask yourself when you start looking at bacterial behavior, which is, how can something this this very simple, single celled organism, how does it know quote unquote when

to unleash the kraken of bacterial infection upon a host? Right, Because even even bacteria that can typically be very dangerous to us are not always in their dangerous state. There there's a few factors that go into whether or not bacteria make you sick, and that includes, um, whether or not they're pathogenic, which is whether or not they're in like attack mode, and how virulent they are, which is, um, how little stabby, Yeah, that's a good way of putting it. Yeah,

And are they angry? How hungry are they? And sometimes it's just that they have to wait until the population is a certain size and then that's when they unleashed the dogs of war or the cracker however, whatever you want to I'm gonna just keep saying unleashed stuff. It's like you're you're you're playing StarCraft and you're trying to save up for a zerk swarm right right, and you just you know there's going to be one. You just

you're not sure when. And you know it's not gonna be something like You're not gonna have a case where it's just one or two things coming at you. It's just gonna be a mass of them. I I apologize if I said that wrong. I've never actually played star Craft.

I just know that's a thing. You just lost cred with pg O. You're like way ahead, all right, so so so yeah, So it turns out that bacteria, despite not having a brain or even a cell nucleus, communicate with each other, and it's in a really interesting way. The way this was sort of observed early on was through um an experiment in which some researchers were using bacteria called Vibrio fisher i, which is a type of

bacteria that is luminescent. When when there are a certain number of the bacteria, then they all uh in sync luminesce they glow. Yeah, so they actually there was a Ted talk we watched in which the presenter showed a picture of a flask of this stuff and it's just glowing green. It looks like, you know, the stuff you would see in a glow stick, but in this case it was just the bacteria that had reached a certain population density. And that's the key. They call it quorum sensing.

And by that what they mean is the bacteria are able to produce the sort of molecular um uh signals, let's say, chemicals that that are essentially saying hey, I'm here and uh. They're called auto inducers, and they also have sensors. This this essentially a receptor that's on the bacterial cell wall. So their message molecules and in ways of detecting right. And so what will happen is if the bacterium is all by, it's lonesome, it sends these

autoinducers out which just float away and nothing gets picked up. Yeah, it's not targeted. It's not like I am bacteria or Bacterium Laura, and I am aiming at Bacterium Jonathan to send a message. It's just like a Hey. It's kind of like imagine that you are stranded on a deserted island and you have your your collection of bottles and collection of parchment, and you're writing down messages and throwing them into the ocean, hoping someone picks them up. Same

sort of thing. Or it could be that you are in a post zombie outbreak safe haven with a radio transmitter and you're transmitting your location in your coordinates and saying, hey, we should we humans should band together, right, But you're doing it, you know, on a frequency that you've picked at random that people may or may not be listening to.

So as you get more of the bacteria cells around the there grows, there's the density that grows of these auto inducer these molecules that are sent out because all of them are are admitting them, right, So you're sending out more and more because the population is growing. When you reach a certain threshold, then the bacterial cells will be able to detect the presence of those auto inducers, and that is the message that to say, hey, express

this gene that does something. In the case of the Fibrio fisheri bacteria, it was to luminess to to glow. Another way that this gene can be expressed, though, is in the production of biofilms, which is something I'm gonna talk about in a minute, right. Yeah, there's a few

different auto inducer signals that can happen. The on and off switch of of pathogenesis um kind of scale of virulence um, the formation of protective spores around individual bacterium which which tell the bacterium, hey, time to bunker down for a minute and hold on uh. And the also the creation of certain substances stuff like that. Yeah, And it's kind of neat because this is not limited just

to intra species communication. In other words, you could have a population of bacteria that can all communicate with one another. The the auto inducers that they are emitting our only keyed to members of that bacteria. In other words, you can think of it like a key that will only fit a specific lock. But they can also emit other auto inducers that are more universal that all bacteria can accept. The microbes are uniting against us, they kind of are.

Although researchers suspect that this thro out of a competition for resources between different species. There's one particular auto inducer called AI too, which a whole lot of species are keyed into. And and it seems like like quorum sensing espionage goes on between species to like try to confuse different different other bugs. You might have one population of bacteria accepting these saying all right, now we know who else is out there, but we're not gonna say anything.

We're we're only going to communicate using our own specific language, and that way we can prepare and unleash the dogs of war one and we can trick them into calming down for a while. Really, So there's also microbial disinformation sort of. It's really more of a decision about whether to communicate or not, right, the idea being like do you reveal that you are there, or do you keep its secrets so that you can build up your resources

to a point where you then switch it on and attack. Um, keep in mind, like there are a lot of bacteria that are very much protective of a host, and then there are other bacteria that can be very harmful. So it behooves the harmful bacteria to kind of keep things on the quiet before going you know, ballistic, right, to have enough of a population to really do what it's intending to do before the host's immune system can figure it out. Right, right, So, uh yeah, we've already kind

of talked about some of these different genetic expressions. There are also cases where the population density actually informs the bacteria to turn off expression. One of these is in cholera cholera, if the population gets too dense, then essentially the message goes out to hey, guys, let's calm it down a little bit. We're going to kill this guy. Yeah, and we want to be able to uh, to spread

this as much as possible. That's our purpose. But if we go crazy, then the host may die as a result, or when in the case of cholera, the victim may end up experience experience seeing severe diarrhea, which then pretty much pushes out tons of the bacteria as a result. So it all depends upon the actual bacteria and what its quote unquote goals are, like what what its survival strategy is, and that determines whether or not it's turning on a gene once it hits a certain density or

turning off a gene once it hits a certain density. Right, So there are lots of different research teams studying quorum sensing and looking for ways to either disrupt it or artificially stimulate it. So they're looking into the chemicals and the enzymes that are used in the process, plus the mechanisms that the bacteria have for creating and detecting these signals. Yeah, and I guess that leads us to the article that

made us want to talk about this today. It was an interesting article in Scientific American from August about what what they called molecular tweeting in the study of bacterial communication. Now this doesn't mean bacteria literally using Twitter are not characters. No, But I wonder I can't come up with a good joke there. I do wonder. I do wonder if they occasionally attempt to tweet out a pizza slice and hopes that Dominoes will deliver to them. Yeah, you haven't seen

those commercials. Yeah, that's a new thing where you can tweet out a emoji of a pizza slice and you order yourself a pizza. But what if it's not the kind of pizza you want? I think you. I think you set up a profile to say what type of pizza you want? Whenever you send that it's not gluten free. Yeah, so this is a new bit of research about bacterial communications.

So it was a team of researchers at Carnegie Mellon University led by the engineering professor du Marculiske, and they wanted to use Twitter as a model to sort of help us visualize or understand different hypes of bacterial communication, how bacteria communicate with each other to form antibiotic resistant superstructures called biofilms. Yeah, this is interesting to me because

it's when you might ask why Twitter. But if you've ever if you ever noticed something, when something begins to trend on Twitter, it's hit a certain density, like a pop culture density within Twitter itself, And that's kind of

what they were comparing the behavior of bacteria too. That if you have enough people sending out this one little message, whether it's a hashtag or whatever, and then it catches on, that could be similar to the way a bacterial UH community sends out these messages to the point where it hits that population density. Yeah, it's a really clever metaphor. And also it is completely scientifically factual that people on Twitter will form UH slimy yet protective surfaces against which

the greater population is protective. I've been there, I've seen it. We should talk about what these surfaces are. What are you're actually referring to. So large numbers of bacteria can communicate with one another to work together to form biofilm that protects them from threats. So a bacterium floating along individually in water is something we would refer to as plank tonic. That's plank tonic bacteria. You can think of it kind of like plankton in the ocean, is little

bits floating along by themselves. They're free swimming. But biofilms are structures that are created when microorganisms like bacteria fix themselves down to a surface and they form dense conglomerations. So instead of using resources to build structures like flagella that help them swim along, they divert those resources and instead use them to build extracellular matrix, which is a kind of slime or polymer film that forms a protective

structure around the bacteria. And these large back sterial films might be thought of as a kind of multicellular organism made out of former single celled organisms. Yeah, it's pretty gross. Especially, yeah, it's gross because they can form inside your body. Bacterial films can be really bad first because they have tougher defenses and they can linger inside the body for a

long time and cause chronic infections. They're much more resistant to your to your immune system, and to antibiotics because of these protective structures and matrices that they form. Yeah, it's sort of like going back to Star Trek, going like like divertal power to the forward shields and then you know, yeah, it's a community of a power grid

adding to a single point of of shielding. Right, But how do brainless, single cell little critters decide to do this, Like, how do they figure out when they can form a biofilm instead of and how that will help? Yeah, So the CMU researchers that we're referred to in this Scientific American article started by observing bacteria in the process of coming together to form biofilms. So they got some bacteria,

set them to work, and observed what they did. And they were trying to observe the specific conditions under which biofilm growth takes place. And then they use that information to make some software that could simulate the behavior of bacteria undergoing biofilm growth. And this is the real outcome of this study is the idea is the idea that we can create simulations of how bacteria communicate with one another under these circumstances, which can help us learn how

to defeat them once and for all. Yeah, I mean even if you could just uh, because we've talked about or or rather, scientists have talked about either replacing or or restricting communication among bacteria as a means to keep them from being able to form these defensive measures or

to uh delay virulence or or not anys genesis. That the idea that if we can mess up their communication lines, then they'll never know that they're at the stage where they could unleash the krackn Right, So what does all this have to do with Twitter? We mentioned Twitter Twitter a minute ago. Well, it was pretty interesting that Twitter user behavior proved to be a really interesting metaphor for three different behavior models that they used in their simulations

of bacteria. So there's let's call them type one through three. Type one bacteria tweets and retweets, and what it tweets and retweets are signaling molecules, those things you talked about in coorum sensing earlier. So it sends out messages to build biofilm, and it relays the messages to build biofilm that it receives Type two bacteria tweets but doesn't retweet. So it sends out messages, It sends out the signaling molecules, but it doesn't retweet the messages it receives and then

type three. This is interesting is lurker bacteria. These are these are the ones that don't post. They don't repost, they just absorb. Yeah, so they sit there and they don't send a relay messages, but instead just create their

own materials to grow biofilm. And according to the Scientific American article, Markliskew is going to be presenting research on this subject at the Association for Computing Machinery Conference on Bioinformatics, Computational Biology and Health Informatics, which is going to be right here in Atlanta starting on September nine, tomorrow, exactly taking place between the time that we record in this

episode goes live. So if he says something world shattering and you all already know about it by the time you hear this, whoops. But well, well, if if it's earth shattering, we will also address it in a future episode where we're like, hey, here's some stuff that happened since we recorded. Yeah, this is all really interesting to me, and uh, a lot of information that I was not

aware of before we started doing the research. Yeah. One of the things that I think is interesting about this is it's yet another example of people trying to create computer simulations to solve problems. This is something that comes up a lot on this show, I think, because and it's interesting because simulations like these are going to be incredibly helpful, but by themselves, they will never solve a problem.

They're just tools that help us work out what we need to test, to figure out how to fight these things right, and how to best use our resources. Because if you just dig in there and you go like, okay, bacteria, let's try sending this chemical at you, then that's that's a less good way of going about your spending your

research time and money. Yeah, and I think it's sort of part of a larger narrative that it's all about modeling the real world and simulation, Like how how close to the complex behaviors of real world phenomena can we get with computer programs. Obviously, the closer we can get, the more we can test in the virtual space rather than testing in the physical space before we know what the answer is. But there's always going to be that

gap between simulation and reality. Yeah. And and also we should mention that even if we really crack the code on this and it becomes a means for us to combat bacterial infections in a new way. There's nothing to say that this is the end of disease or anything bacterial, but even bacterial vectors. It's not the end of disease. Um that's something that is important to remember. But it could certainly give us an advantage in the foreseeable future.

But there's nothing saying that further down the line there won't be another um mutation or advantage that makes this less effective or as dr and Malcolm would say, finds a way. Yeah. Well that's really the bottom line in the story of evolution, in't it, Because we're fighting against evolution and that's a battle you can't in the long

term win. Yeah. You could, actually you could completely eradicate a species, or you could I mean, I guess you could impose limitation so harsh that they come down to the laws of physics and no adaptation. But I mean, like, you can't have an organism that adapts to five thousand degrees fahrenheit. But in most of those cases it requires action so extreme that we would be uh negatively impacting

ourselves in the process. Yeah, and either way, you can never discount the idea that some nice old man who's very fond of wearing cuban shirts and carrying a cane is going to come along and purpose we recreate murderous creatures. Well, we just rewrote Jurassic Park, so wait, hold on, now, the story is that the friendly old billionaire creates. Mr Say. Yeah, he's like everyone in the world has the chance to enjoy this. Mr Say, I'm ready. I'm ready to call

it right now that amusement park is gonna suck. Well, oh, they just built the bolowing lick this surface. Well, with that in mind, I will invite all of you to infect us with your ideas for future episodes. If you have any suggestions for topics that we should cover in future episodes of Forward Thinking, whether it's the podcast or the video, you should let us know. You can send us a message to our email address as f w Thinking at how Stuff Works dot com, or drop us

a line on Twitter, Facebook or Google Plus. At Twitter and Google Plus, we are FW thinking, search FW thinking and say books search bar. We will pop right up and we'll talk to you again. Really sick for more on this topic and the future of technology. This is forward Sinking dot Com, brought to you by Toyota. Let's go places