Rediscovering Biology: Molecular to Global Perspectives
Microbial Diversity Expert Interview Transcripts: Bill Costerton, Ph.D.
Director, Biofilm Center
Costerton is the director of the Center for Interfacial Microbial Process Engineering at Montana State University in Bozeman. His work delving into the differences between floating and attached cells has revealed both the presence of extracellular matrix material surrounding attached cells and the ubiquity of slime-producing attached bacteria in natural systems.
Costerton is the director of the Center for Interfacial Microbial Process Engineering at Montana State University in Bozeman. His work delving into the differences between floating and attached cells has revealed both the presence of extracellular matrix material surrounding attached cells and the ubiquity of slime-producing attached bacteria in natural systems.
Can you talk about how people used to think about bacteria and what we know now about bacteria?
The first revelation in the biofilm field really came from mountain streams, because we used to find eight bacteria per ml in the mountain streams. Then we looked on the rocks and surfaces in the stream and found 10 to the 5th, 100,000 bacteria per centimeter squared. We used to think that the predominant bacteria were swimming and now they turn out to be less than 0.1% of the population in most systems.
The basic concept in environmental research and medical research was that they were all swimming around independently. They couldn’t be associated for very long as they swim past each other. But now in the biofilm concept, they are right next to each other-they can stack up and organize communities and that’s a huge difference. So basically in the environmental area and the medical area we used to think of them seething around. But they are actually growing in highly organized communities, which is a very major switch.
When did that all come about?
It was sort of progressive. We first looked at a stream and found they were mostly on surfaces. I tried to extrapolate very quickly to medical situations and really got crucified for it. The medical people said, no, medical bacteria probably would be different, so we don’t believe it. I went back and got three more years of data and it turned out to be right. By about 1995 almost everybody was looking at bacteria as being predominantly in these biofilm communities.
So following up on that, they aren’t really these primitive single-celled creatures that live by themselves? Right?
The first thing we saw was really fun because we saw them on surfaces and we presumed that they were in slabs in a not very organized way. But then we started in 1993 looking in a lot more detail using the confocal scope and we could see they were in towers, mushrooms with channels between them. Then it started to get really interesting because if you run it backward in your mind, you can’t make complicated community unless you have signals and organization in some way. At first, it looked like they could be pretty much loners but in a stack. Then when the stack showed out to be really differentiated with different shapes and things like that then we knew they had to be talking to each other and had to be a really complicated community with the equivalent of hormones and pheromones, which is a total revelation.
What is a biofilm?
We’re still at the end of a descriptive definition of biofilms, which means slime enclosed by a bacterial population on a surface. But as we go more and more. Molecular, we find out that they are actually different, the genes they are expressing a very different indeed. As different as a seed is from a mature plant. So it’s almost like the swimming bacteria, the planktonic ones, were the seeds. The genetics are very different. We’re starting to define biofilms in genetic terms now. But for the meantime we’ll stick with the old definition, that’s slime-enclosed bacteria on a surface. A biofilm is a microbial community enclosed in a matrix material located at a surface.
How has the shift changed, to understand them more at a molecular and genetic level?
At first we were descriptive and basically we thought yes, they are more or less individuals, but they happened to be trapped on the same surface together. Then that offered no new opportunities for things like therapy. But right now 65% of the infections seen by doctors in the developed world are of the biofilm type. The big problem is they are very resistant to antibiotics because they are expressing different genes from the floaters against which the antibiotics were first designed.
So as we know more and more which genes are being expressed and we know how these critters are communicating with each other, we can neutralize particular proteins that they make which is a huge advance on infections that are biofilm infections, like kids’ middle ear infections, cystic fibrosis, prostitis, and lingering infections of almost all kinds.
This sounds like a revolutionary way of looking at biofilms, what was the tool that helped you?
Almost all the preparative methods for looking at bacteria involve taking them out and fixing them, the things we’ve done for hundreds of years in microscopy. But the confocal microscope came up in the 1960s for botany and zoology and microbiologists never used it. Because after all if you’re in a single cell, you don’t need a fancy microscope, you just need a very high-resolution microscope. This has a laser beam going back and forth, quite wonderful and I can actually remember when we cranked up the confocal microscope in the first afternoon in I was in the center. We got this absolutely amazing thing to look at and it was water channels running all the way through the bacteria, because you are looking at a live biofilm by confocal. A living biofilm, fully hydrated, not fixed in anyway, not collapsed in anyway, an absolutely true image. Just blew the whole thing away.
How does the confocal microscope work?
What the machine does is it actually looks at one focal plane and then drops down to the next one so you see a sequence of optical slices as they go right down to the surface, which has been colonized by the bacteria. So if it was about a 50-micron biofilm you’ll see slices going slowly across. Then you can take that image and compile it and bring it back into a 3D image and then you can roll the image, you can look at it in the XY or right angles, which is the Z-axis. So confocal is fantastic and there are no preparative difficulties.
What are the different types of biofilms?
We always look at microbiology from a human point of view. There are good bugs and bad bugs, but the bacteria don’t know which are good and which are bad. For example P. aeruginosa is the predominant organism in alpine streams or any cold water systems, salt or fresh, it’s a very common organism. But it becomes a pathogen of cystic fibrosis; it doesn’t behave any differently in cystic fibrosis from what it does in the stream. Lots of bacteria make biofilms, they do their thing and it might work out well for us and it might work out badly for us but they have exactly the same strategy in every case.
So let’s talk about some of the ones that are really useful. The best one of all is in the female reproductive system, lactobacillus. We study that biofilm a lot for one of our companies, the tampon manufacturers. Basically it’s extremely protective because the tissues are just covered in lactobacillus in a biofilm, they make a very acid environment. Other bacteria have great difficulty getting through and that’s in fact why the reproductive system is as successful as it is.
What types of surfaces do biofilms like to grow on?
The surfaces are almost all the same to them. We dreamt for a while that the whole process of adhering to a surface might be very specific and we might be able to find the “magic surface” that bacteria couldn’t adhere to. A lot of companies spent tens of millions of dollars looking for that surface. In fact, they got a few false leads that led them in that direction. There is no bacteria, biofilm-proof surface. There is not going to be one either, for theoretical reasons. They love inert surfaces; they come down onto the surface. They don’t care if it’s rough or smooth, it’s oily, soaped or whatever. They just jump on in huge numbers.
The surfaces they have difficulties with are intact, healthy tissue surfaces because those surfaces are booby-trapped with all kinds of really bad things. Before the biofilm can form these incoming bacteria have to survive, if there are antibiotics, antibodies they can’t survive. For example, [your eye] is one of the very best defended tissues-every time you put in a contact lens [from] the holder where it’s been festering and the chemicals are old, you probably got a little biofilm on the lens. In 15 minutes the tissues of the eye have killed all the bacteria on that lens and cleaned it for you.
That’s amazing. The eye cleanses it for you?
Several of the molecules we work on do this; one is called defensin, which is a wonderful word for a protein. Another can kill bacteria, so you can put a pretty dirty lens in your eye and I can take it out 20 minutes later and find out all the bugs are dead.
A healthy person can slough off the bacteria: But what happens with someone whose immune system is compromised?
They get into very serious trouble, we do understand the cystic fibrosis (CF) thing quite well. If your larynx, or the back of your throat, is colonized with bacteria, a little cluster of bugs that we know quite well, fall off and go into your lung: they can’t set up an infection.
But in a CF kid, before his lung gets infected, the whole larynx gets covered in Pseudomonas, it’s a difference in the secretion patterns in the CF kids. My son has cystic fibrosis and you can actually smell the pseudomonas on his breath ever since he was born, at a pretty early stage.They can’t slough it off: their bodies make a big biofilm and then lumps of this biofilm go down and challenge the lung rather than just a few bacteria at a time. It’s a big goopy kind of a mess. Maybe 100 cells with slime around them, head down into the lung and the white cells in the lung can’t handle that kind of challenge. They can handle a few bacteria in a few minutes but they can’t handle these big lumps.
What happens with some of the surfaces, like artificial implants and why are biofilms a problem for these artificial devices?
Any plastic or any metal is really susceptible to being colonized by bacteria and getting a biofilm going. Of course they don’t stay just on the plastic and the metal for very long, they very quickly get serum across the surface of them. Then the bacteria see the body coatings and a nice, flat surface with no defensive molecules around and they jump all over it, and build up a biofilm very quickly. So in the urinary catheter, the chances of biofilm formation and infection are about 10% per day that the catheter is in place. So if it had it for 10 days you have a 100% chance of getting an infection.
It’s an awful problem. Actually [for] a whole industry; things like the artificial heart, for example, were successful physiologically, but they were not successful in keeping bacteria off. So actually the artificial organs and the spare parts industry have been held up now because if you make too complicated of a device the bacteria will eat your lunch.
So they are making them less complicated?
[They are using] different strategies, like replacing the left ventricle rather than the full artificial heart. You don’t get so much colonization. The strategies are getting better and better but the bacteria are winning most of these.
And why is that? It seems like these infectious biofilms are all very difficult to treat. Is that correct?
Well there are three different things we depend on, antibiotics should be working and they aren’t. We now understand that this different gene expression in the biofilm is a large part of that. Antibodies should work. If you have cystic fibrosis and you’ve been living with it for 35 years, as my son has, you have lots of antibodies against the pseudomonas but they are in these slime balls, and the antibodies are circling around the outside of the slime ball and they are not working. Then the white cells should actually be picking them up and killing them. It’s a sort of a standoff for very long lengths of time. So you end up with a very long-lasting, chronic infection.
Why can’t the white cells clear the bacteria out?
We thought up lots of complicated explanations and it finally hit us in the face. Because single bacteria are about one micron in size and a white cell is about 15, they can take them in. But if you get a biofilm that’s about 100 microns in diameter, a big mass, then the white cells come along and try and nibble away at it. When they can’t internalize it, they do a very nasty thing, they sit back and fire enzymes at it. Bacteria in the biofilm couldn’t care less about the enzymes but the surrounding tissues get quite damaged.
The argument with antibiotics is, when they are trying to attack a biofilm all the bacteria in the biofilm are in different physiological states, is that correct?
Bingo, that’s it exactly.
What other factors make it difficult for antibiotics to attack a biofilm?
Floating bacteria are generally the same, they are either growing aerobically, fast-growing or slow-growing but they are pretty much the same. Whereas in a biofilm, there are some that see oxygen, there are some that see absolutely no oxygen at all. Some of them are growing fast, some aren’t growing at all. So you can’t kill all these classes of bacteria with the same antibiotic. So an antibiotic comes through and kills all the ones that are growing aerobically if it can penetrate and then the biofilm can just re-grow. Then it can come through and kill all the fast-growing ones-penicillin does that. Then the slow-growing ones will just take over and grow back. You can never kill all of the different categories because there is so much variety in a biofilm.
Do antibiotics target more quickly dividing cells as well?
One of the classic antibiotics, penicillin, actually only attacks growing cells because it attacks the mechanism whereby the cell wall gets bigger. It’s called a penicillin-binding protein and in fact, it’s building a new cell wall. If the cell is just quiet then the penicillin has no effect at all. So non-growing cells are totally resistant to penicillin. Not all antibiotics work that way but that particular one works that way.
[In biofilms,] the cells on the outside are used to growing a bit faster. They are used to nutrients if they are aerobic, they see more oxygen.
Can you discuss the stages of a biofilm from start to finish in terms of genes being turned on and off?
The very first thing that the bacteria have to do is come along as planktonic cells. They have to make a decision to stay on the surface. Otherwise, they are popping on and off all the time. So when they irreversibly adhere, then they start a process where they start to turn a bunch of genes on and that’s within 15 minutes of first adhering and we know a bunch of those genes. They are slime producing ones and all kinds of interesting ones. Then to our absolute amazement (this only happened three years ago) we noticed how many genes they were changing. They actually change 70% of their gene expression.
So planktonic cells making certain proteins, expressing certain genes, compare that to a biofilm after about 4 or 5 hours after it’s formed, 70% of the genes have changed, turned off or turned on. Now we have a whole new set of proteins and a whole new set of gene products.
How do they decide to stay? Do they have a sense of touch?
We don’t know the mechanism whereby a cell actually makes this final commitment. It’s a great place to be on a surface-there is more food. We have just one idea and that is, if you’re a cell in fluid then any molecular release would be equally diffusing away. Whereas when you come down onto a surface then escaping molecules are kind of trapped in a hot spot underneath the cell. We have that idea, but no real proof for it yet. So then when they make the decision they kick in slime productions so that they can cement themselves in place. They are going to come together and make towers and surround themselves and leave certain channels open. They eventually build something sometimes as thick as a millimeter. The tartar on teeth is at least a millimeter thick some mornings.
If they decide to stay, the genes that make the flagella are no longer used?
Bacteria, when they are floating, have a flagellum, their organ of swimming. They also have some pilli, which are sticking out. They need to turn those off because they don’t need them anymore. So that gene turns off, the number four pillus turns off, and we can watch them turn off. Slime turns on and we can watch that one turn on we have a reporter system where a color change happens. But the bombshell was that they change almost everything. We were expecting them to change maybe ten percent of their genes and they change 70%.
After they successfully attached, how soon do they start producing the extracellular polysaccharide matrix?
What they do is come down and maneuver into position on the surface. They have done that and stopped moving and within 15 minutes they turn on a gene called algC. Then with another bit of research we did, [we found] two related genes D and E. All three of these turn on.
Now we’ve got a reporter system where we can watch it happen because a color change happens. When it comes down it changes and the yellow color comes up so we know the genes turned on. We can actually see the slime starting to be produced by the cells. And if seven or eight of them are doing it, they slime together. The package is firmly anchored on the surface and by that time they are way on their way to making a biofilm.
When the cells start banding together how do they know how to turn these genes on and off? Are they talking to one another?
This was a discovery that was made about 20 years ago in planktonic cells in a marine system. [The researchers] thought it was just a freakish thing that happened with this particular species of vibrio. They can sense a quorum. Quorum means a number of individuals together like we would use in terms of a meeting. If there are 2 or 3 together they do sense a quorum and they turn on all manner of things through quorum sensing.
Basically, if there is just one and it’s giving off a few of these chemical signals they kind of diffuse away and nothing much happens. Then they reach a certain, critical concentration, which they reach because there are quite a few cells there where everything turns on. This quorum was first discovered in a marine organism (a sea squid) that is fluorescent. The bacteria don’t bother fluorescing unless there is enough of them to make a difference. So they switch on when there is a quorum. We thought that was just fluorescence and just the marine system. If we [had] guessed and taken a chance and said, hey these ones are sensing a quorum, I bet they’re all sensing quorum, we would have probably found out what we know now, 15 years earlier.
It sounds like they have to be a high intelligence being in order to do this.
We are reclassifying bacteria. The biggest single thing is that we’ve gone from bacteria being little pre-programmed bullet-like things to a huge community with all kinds of sophisticated controls. The image I like the most and I’ve used it in a recent review is it is like botanists that studied seeds for about 150 years and never actually discovered plants. You know you have a seed and it’s got the whole genome and everything. It flutters down and does all the things that seeds do but you didn’t ever discover the tree or the bush or the flower. It’s sort of that magnitude of break we have now that we go from these simple things to organized communities all in a very short length of time.
You talked about water channels, how long does it take a biofilm to make those?
[They] start off with a bunch of microcolonies on the surface. One here and one some distance away, and they grow up in either mushrooms or towers and some more come up. They leave a space in between themselves. They are able to do that by chemical signaling and we don’t know exactly how they do it. But basically they leave a space between themselves. Then a really interesting thing happens and we are just starting to understand this: some of these towers and mushrooms get too big to be really functional and when they get to that point they return to the planktonic form. It happens in the middle of the mushroom head and they go liquid and start developing flagella and they are all seething, we call the behavior. Then that big mushroom just collapses down and all the bacteria take off. Now that makes a channel when they do that. So, the channels are left behind as the towers come up and are somewhat controlled. Then if it gets really thick, like an endoplaque, some of the actual elements like the mushrooms and towers dissolve, swim off. Then you have a great big channel.
So it’s not worth it at that point to be in a huge biomass anymore? They turn the genes on so they can swim away. They aren’t making a good enough living?
We have one piece of evidence for this that really is quite strong. We call it stagnation. If we have a population that has a bunch of incoming food and quite a bit of oxygen, it does not have much stagnation, and very little detachment. But one researcher discovered that if you shut off flow and left it off for about 4 days, then it went stagnant and all kinds of these different mushrooms and towers were developing planktonic seething, breaking down, and the cells would take off. Of course, they go to find a new and better environment. So it’s the right move made by the bacteria in a highly organized way.
Again how do they do that? Are genes turned on that tell them to make proteins to help them swim away?
I think I know, but I’m guessing. I am cantering out into space a little bit on this one. We know that there is a signal and a particular code that is somehow connected to this. I keep thinking if you were in a mushroom and there was quite a bit of flow and you were making this signal it might get washed away. Then when stagnation happened it might build up in concentrate: on good days we can inject a little in there and get the detachment thing to work. So there is a sort of a plan where flow takes away the signal so if you’re flowing you don’t get any detachment. When you stop the flow, the signal builds up to a certain concentration and changes the biofilm cells into planktonic cells and they swim away. That is my best guess as to how it happens.
Can you to talk a little bit about these mushrooms or these big communities. They are micro colonies?
The mushrooms-we call them micro colonies-are mushroom-shaped or tower-shaped, they are 85% matrix and 15% cells. They are fairly rubbery. The cells at the bottom and the middle of the mushroom head aren’t seeing very many nutrients and oxygen. So by that time they are just hanging on like grim death. You wouldn’t have any nutrients getting to the bottom of these big things if you didn’t have the water channels. So it’s like a primitive circulatory system. It’s bringing in nutrients and removing waste. It’s been likened to the streets in a major city. It brings communication through that let things get transported back and forth.
Can you talk about biofilm transformation?
We’re used to thinking in terms of single species, so let me go through with the single species first because we have to remember that in very few environments we have just one species of bacteria. So it’s planktonic and it comes and builds a biofilm and they can come up into the mushrooms and the towers and so on. It sees food come in and it builds the large structures. It can turn into planktonic cells and detach. It has a life of its own as a community.
Now that’s very rare in nature. Alpine streams have one species, pseudomonas. Most things, like the mats you saw in Yellowstone Park, have thousands of species. There, the biofilm is actually a unit within which they can cooperate. If you have photosynthetics, fixing sunlight and making sugars for example, bacteria can hang around those. Then right at the bottom of the stack are some poor starving devils doing the last thing and making methane, which is a very unhealthy way to make a living. So basically in the biofilm you get these cooperatives set up.
We study a number of these cooperatives. The one I love is the one in sewage treatment that finally gives you methane. The bacteria on the outside of an aggregate take organic material and break it down. Then you have a layer inside that is actually using acetate and making free hydrogen. They are feeding it to the ones in the dead center who are taking the hydrogen, adding it onto carbons and making methane. Then there are these burp holes that come out through these aggregates. Methane burps out and they keep making methane in huge amounts. Engineers who handle these systems love this because they first get these poppy seeds, and when you get a real good bunch of poppy seeds working for you your getting wonderful transformations. And they are organized. That is the epitome of a good biofilm; you just don’t have one species making elaborate structures. You have structures coming up where the right neighbors got together and they can do fantastic things like change organic sludge into methane.
It almost sounds like there is a division of labor within this community.
The characteristic of a complicated organism is that there is a division of labor, all the cells are not the same. We have liver cells and eye cells and so on. We used to think bacteria were essentially the same. We find that one species is making acetate. The next one is making hydrogen. The next one is making methane and they are right next to each other. There are two big schools of thought and I know which one I’m in but I can’t prove it and the opposition can’t prove their point.
One school says, some bacteria are making acetate so one that uses acetate and makes hydrogen is going to cozy up to it just because it’s the best place to be. The next one is going to strip the hydrogen off and feed it to the methane. They sort of get together because it’s the cushiest place to be. I don’t buy that for a minute. I buy that it signals, “acetate for sale.” And then they come in and the whole thing is thoroughly organized- it isn’t just going to this location. They take up these positions before the machinery gets going. So before any acetate is being drained off, the user is right next to the acetate producer–than it’s all programmed. Very much like tissue development is programmed in higher organisms. There is going to be another 100 years of working this all out.
I think it’s all going to be signaling-I’ll bet there will be thousands of signals and they will be talking to each other in great detail. The nice thing about it is, if bacteria are causing you problems, you can start to jam their communications and they couldn’t be as effective.
Particularly in disease and biofilms with cystic fibrosis patients, why is it so important to think of this as a whole different organism? What are the ramifications if you don’t?
We’ve actually found the ramifications if we don’t think of them as communicating beings. The only option we had before [was to] interfere with them or manipulate them in any way. We’ve been trying to do that since the 1930s with various antibiotics and they get really pretty panicky when everybody is out to kill them. So they throw up their defenses and we have resistant strains.
But now there is a fantastic development. Naomi Balaban at Tufts in Boston has discovered a blocker for one of the signal molecules, and she can take staphylococcus and just hold it in a not very pathogenic form and it’s almost planktonic. It’s not making any toxin, [and is] pretty susceptible to antibiotics. She keeps it from making the shift to biofilm by blocking the signal. The blocker is called “rip” and the signal is called “rap,” which is kind of cute. She’s actually done this with animals: she’s put staphylococcus in on a foreign body into the animals and if she puts the inhibitor in, the bacteria don’t get full biofilm formation and they still stay susceptible to antibiotics. Therefore she’s locked them in the susceptible position.
But there is a whole new era where I think we’ll know certain genes are being expressed in biofilms. We can make antibiotics specific against those genes. But the most sophisticated step would be to figure out what signal is controlling the bad activity of the bacteria and block it.
By bad activity you mean the best thing to do is block the genes that help them organize?
That’s the more detailed way of doing it. Or we could find a signal that activates maybe a cluster of 10 or 12 genes. So if for example, we had toxic shock or something like that. We know what signal turns on that set of genes-we can’t block the individual genes, but probably the better thing to do is block the signal. Block the signal then the bacteria can grow, have a nice life, but they don’t make the toxin.
What’s another strategy we can use to combat biofilms?
There are two kinds of strategies that can be used. One of them is that you stop making the biofilm community completely, that is you just keep them planktonic. Somebody has discovered a blocker that does that, it’s made by seaweed in Australia, a red, algal seaweed. It never gets biofilms on it, so it’s perfectly clean even though everything else in the marine environment is coated in biofilm. It blocks the biofilm-making system. [It is] being incorporated into marine paints and the US Navy is looking at it for their battleships.
[The] second strategy is to just let bacteria grow and keep it from being toxic, in the case of toxic shock, for example. If you’re wearing a tampon and that tampon has got blood on it, staphylococcus loves that environment. There is nothing wrong with having staphylococcus there as long as it doesn’t make a toxin. So let’s take a hierarchy here, one signals turns on maybe 20 genes that make the toxin. We could start playing around with these 20 genes, but the most economical way is to stop the signal that turned on the 20 genes to start with. If we know what that signal is maybe we can block it. The bacteria would grow with no problem at all, you’d throw it away with the tampon and you never would have made toxin. That’s the more sophisticated technology as I see it.
Where are we with developing compounds to help CF patients, to help stop the biofilms from growing?
Well this is amazing and the question, of course, is perfectly well-timed. It’s just coming out right now, in the next couple of months. That signal that was discovered in Australia was discovered partly with the help of people in Denmark who are in the cystic fibrosis clinic. They took a mouse model of cystic fibrosis and treated the mice with this particular compound that discourages biofilm formation. I never thought that it could reverse the process. In other words, I thought that when a biofilm was formed, a compound couldn’t break up the biofilm. But they have had extremely exciting results in the mouse model. Where a chronic infection was just going on for months and months wasn’t killing the mice but it was just like cystic fibrosis. The chronic infection went acute and was curable by antibiotics and in two cases of about 15 mice they were able to free the mouse model of pseudomonas. Now, it’s not a perfect model for cystic fibrosis and a mouse isn’t a human. Were not there yet, but it’s a flicker that says we can change the way the bacteria inside an animal are growing with a blocker and I get wildly enthusiastic about that.
What questions do you need to answer to get where you want to go?
We have actually had three huge advances in my time here as Director of the Center. The first one was the water channels on all the complicated structures. I think we’ve got that one fairly well understood. The next one was signals. What we have right now is an idea that if we totally cut off signals or block all the signals, something happens but we don’t really understand the mechanism. We are just going to have to keep on going, finding more signals and there is room in here for thousands of people to do this kind of thing. Then we’ll finally fill in the whole story. It’s like in the human we understood growth hormones and insulin but we hadn’t discovered thyroxin or something like that or oxytosin. It’s the tip of the iceberg. All we can do now is throw a big hatchet into the works and say there is an effect but we can’t really get the subtleties of the whole thing down in there.
What is the importance of having more biofilm research?
Let me just take the impact factor here. If you really wanted to do a great deal of good for mankind, you are not going do that by simply coming into a well-worn specialty and being one more practitioner of that specialty. People sometimes have an aneurysm in an artery. So surgeons chop out that piece of artery with the weak wall and put in a Cortex or a Dacron sleeve, called a graft. They’re fine and they work in most cases, but about 4% of them get infected-a biofilm starts to develop around where the stitches are and the stitches pull out and that breakdown and you would die in about two or three minutes after it’s let loose.
So, we’re working with some people in Italy-and they thought of this, I didn’t-and that was if a biofilm gets going and the biofilm proteins are different from planktonic proteins, we should be able to pick up antibodies to them in the patient. We can say, yes, this graft is biofilm positive, go in and preemptively cut a larger section out and put a new graft in and probably save a life.
The next one is [with] vascular catheters-when they have to change one because they think it’s causing infections, they actually run a wire with a little J cap on the end of it. They pull the old catheter off and put a new one down the same wire so it goes to the same place and then just pull on it-the J straightens out and you’re changing over a J wire. Because we understand biofilms, this is a genuinely bad idea because when the J wire went down it, it knocked off all the biofilm, which is going to go into your lungs or your brain and cause all kinds of problems. And of course, the new catheter is going to get inoculated from the old one. So just understanding that there are biofilms in these chronic device-related infections changes certain clinical patterns-it changes the way you handle them.
Therefore, if you went into medicine with that mindset, you could actually spread some new information there. And if you went into a pharmaceutical business and picked out an antibiotic that worked for cystic fibrosis, middle ear infections, and prostatitis, you would actually have made a massive change in the practice of medicine.
[Scientific] fields go along with bursts in them and now there’s a burst in microbiology. I’ll submit to you that while microbiology is a fairly minor science, that is, not too many people go into it — this jump in perception in microbiology is almost unparalleled in the history of science. Where there was an old way of looking at bacteria and now there’s a new way of looking at bacteria, and if you catch that wave, you can go a long, long way on it so that’s what gets me excited.
Educationally, we’ve been able to do lots of genetics of bacteria quite nicely on planktonic cells because they have the same genes. But let me give you an example in the medical field that is very discouraging. Right now when doctors are treating kids’ middle ear infections, they get results back from the lab that say, “We couldn’t grow any bacteria. It might be a virus.” But the doctors know by experience it isn’t a virus; it’s bacteria. But they were growing it in a biofilm and none of them happened to let go and they therefore didn’t grow on the plates. And then if they do grow they’ll grow them up as planktonic cells and say that they’re susceptible to certain types of antibiotics. They’re going back to clinical experience to actually treat the kids and totally ignoring the results of the microbiology analysis. And they’re right because the old microbiology is working with planktonic cells, identifying the wrong antibiotic, missing bacteria when they’re present. New methods are necessary to correctly diagnose and correctly pick out the right antibiotic and the doctor’s always good at this. They know what works and what doesn’t work and they have hundreds of patients and they work out a strategy.
But the clinical lab in microbiology is ignored more often than not, and so this is a tremendous time to come into a field like this and make a huge difference in the medical field, if in fact, you started using these methods.
So there’s regulatory, there’s educational, there’s the medical stuff, and there’s engineering and all kinds of things. One of the great things about biofilms, of course, is they happen in so many fields and they happen in so many geographies that I get to look at biofilms on tropical coral reefs; I get to look at them in sewage disposal plants, desalination plants on the coast of Saudi Arabia, I get to look at them in the medical, just about every area.