Here, at Princeton University, a team are taking a radically new approach, one that has led to an unexpected breakthrough in the fight against deadly bacteria. Professor Bonnie Bassler has spent her career discovering the hidden world of bacteria secrets.
Professor Bonnie Bassler “I love bacteria. I think most of the things they do on this earth are fantastic and essential, but bacteria have features, bells and whistles, different processes, that they are, that they have for fighting in their own environments. And when those get unleashed in a human or in an animal or in the plant, it can kill us.”
With antibiotics, we have been attacking bacteria, forcing them to evolve resistance. But Professor Bassler thinks that we may not have to be so aggressive.
Bonnie Bassler “Instead of just smashing them to smithereens quickly done with traditional antibiotics, if we could learn enough of their secrets, and get them to spill their guts a little bit and tell us how they work, we could just get them to behave. And do behaviour modification instead of killing them.”
Compared to us, bacteria are so incredibly small On their own, they shouldn’t be able to hurt at all.
Professor Bonnie Bassler
Bonnie Bassler “If one or a few bacteria release their most deadly arsenal of toxins, they have no effect. I mean, this is not David and Goliath, this is like way beyond that, so the question is, how can these bacteria have us on our knees, right, how can it be that they can actually kill us?”
Bacteria don’t attempt to attack us on their own, they wait until there are enough of them and then act all at once.
Bonnie Bassler “You can think of the bacteria, each individual bacterium as a soldier, and so you have these masses of soldiers, but is only useful when somebody says ‘charge’, right, so the question is what’s the information that tells the bacteria now is the time to attack?”
If we could find a way to stop the bacteria attacking together, they wouldn’t be able to harm us. But understanding how they coordinate their attack is incredibly difficult because bacteria are hidden from sight. But there is a type of bacteria that you can see, and they have a rather unusual relationship.
Hawaiian bob-tailed squid
The Hawaiian bob-tailed squid is a master of disguise. In the day, it disappears into the sea bed, but when it comes out to feed at night, it’s even more ingenious.
Professor Bonnie Bassler “At night, this is like the Stealth bomber of the ocean, it likes to cloak itself in an invisible device. If it would just swim around, the Starlight or moonlight would hit its back and it would cast a shadow on the sea floor and then predators that could see that shadow could calculate its trajectory, and eat it.”
To eliminate their shadow, these squid project light down onto the sea floor.
Bonnie Bassler “By matching how much Starlight or moonlight hits it’s back with how much light comes out of its body, there is no shadow. So it’s a fantastic sleight of hand, sleight of tentacle, if you will, it’s a fantastic anti-predation device because it makes it invisible at night.”
And this incredible invisibility cloak is created by bacteria.
Professor Bonnie Bassler “There is a bacteriuim that lives in the body of the squid, the bacteria’s name is Vibrio ficheri, and it makes light, so the squid gives the bacterium a home, bacterium gives the squid light, and the squid uses the light to protect itself from predators.”
But just as a single dangerous bacterium would not be enough to make us sick, the single glowing bacterium would never produce enough light to help the squid. For the bacteria to be useful, there must be lots of them. So the bacteria wait until there are enough of them, only then, all start glowing exactly the same time.
Bonnie Bassler “When this was initially discovered, the idea that bacteria can do something as the group was revelatory.”
The bacteria were working together, question was, how were they doing it? The beauty of these marine bacteria is that they glow in the dark, so we could experiment to see what exactly caused them to start making light. They discovered the bacteria were producing a chemical messenger – they were talking to each other.
Bonnie Bassler “As they grow and divide, they all make and release these molecules. When there’s more cells, the molecule outside cells increases in proportion to cell number. And when the molecule gets a certain amount, the bacteria have receptors on their surfaces, they detect that the molecule is there and then they all change their behaviour in unison.”
Using these molecules, the bacteria were able to detect when other bacteria were around them. And by communicating with each other, the bacteria were able to achieve something we could never achieve as individuals. This behaviour is called quorum sensing.
Professor Bonnie Bassler “Sometimes, the way I think of it, is if you want to move the piano from over there, to over there, you don’t try to do that yourself, you get all your friends, everybody grabs and you say, ‘one, two, three, lift.’ And then you carry out this task as a coordinated synchronous group that you couldn’t do, if you are just acting on your own.”
Once they’d discovered the glowing bacterium could talk to each other in chemicals, Professor Bassler began to wonder if this was the way dangerous bacteria were coordinating their attack.
Bonnie Bassler “Well so I thought, well I wonder if anybody else makes this molecule. So I just collected every bacterium I could get my hands on. And every bacterium I’ve tried that with, it worked. And there was this moment, I still get goose pimples with that, there’s this moment where I thought, Holy Cow, they’re talking between species, they all make this molecule.”
It looked like all bacterial molecules could communicate using these molecules. This had incredible implications. If she could interrupt these conversations, she could get the bacteria to stop the group behaviour.
Professor Bonnie Bassler “We know what these molecules are, at least some of them, these quorum-sensing molecules, so we’ve made antagonists, right, molecules look kind of like the real things, but they jam the receptors. And so if you add those, it’s like static, you know, you add these anti-quorum-sensing molecules, the bacteria can’t hear.”
Professor Bassler had found a way to stop the glow-in-the-dark bacteria from talking. Could she do the same with dangerous bacteria and prevent them from launching their attacks?
Bonnie Bassler “We started this work with Vibrio haveri and Vibrio ficheri, this beautiful bio-luminescent bacteria, but they have a nasty cousin, Vibrio cholera. Those two bacterium make this beautiful light, this guy kills you.”
Also completely eradicated in the UK, the cholera bacteria is responsible for over 100,000 deaths in the developing world every year.
Bonnie Bassler “So we transferred what we learned from the glow-in-the-dark bacterium to this bacterium.”
Professor Bassler can measure the level of a protein that cholera bacteria produce that makes them deadly.
Bonnie Bassler “This is the protein that, makes that, lets it adhere to your intestine. It has two make this. It’s step one in the infection and that makes it virulent. So then what we did was, we added our anti-quorum-sensing molecule at different amounts to cholera cells, and if we add more and more and more of our molecule, what you can see is it makes cholera incapable of making that virulence protein, and incapable of making an infection.”
This is just the beginning for Professor Bassler and her team, as other researchers around the world are now investigating whether this method of silencing the bacteria has the potential to work where antibiotics are failing.
Scientists have entered a new stage in the battle with superbugs. It may be that we have underestimated our enemy.
Clint Murray “They’re probably smarter than I am. They’re able to justify fire much quicker than I can show they are able to develop resistance whole lot faster than I can develop an antibiotic.”
But around the world, scientists are taking up this cat and mouse challenge.
Roy Kishony “It is a game, they’re playing their game and we need to play our game. We each need to do our best move.”
We are understanding these entities better than ever before but maybe we don’t have to triumph overall, we just have to stay one step ahead.
Bonnie Bassler “We don’t have to totally win, that’s not the goal. The goal is simply to find out enough to be able to do something useful and then let the next science find out the next thing that’s enough to do something useful.”
Bacterial Sex Secrets – Oxford University