A Sweet New Treatment For Antibiotic Resistant Infections?

IRA FLATOW: Our next story is unexpectedly sweet. I’m talking saccharin. Researchers have discovered that the artificial sweetener has powerful antimicrobial properties. Tests suggest that saccharin can actually kill antibiotic-resistant bacteria and, with the help of traditional antibiotics, may even be used as an effective wound treatment.

Joining me now to tell us more about this fascinating research is Dr. Ronan McCarthy, Professor in Biomedical Sciences and Director of the Antimicrobial Innovation Center at Brunel University of London. Welcome to Science Friday.

RONAN MCCARTHY: Thank you very much for having me.

IRA FLATOW: You’re welcome. I’m fascinated by this. What would make you decide to look into saccharin? I mean, what made you think this might have antimicrobial properties?

RONAN MCCARTHY: No, it’s a great question. So my lab actually has a history of looking at compounds that are present in the diet and exploring the impact that they have on bacterial behavior. Bacterial communication. And when I started to look into the history of artificial sweeteners, I was really surprised to see that many of these were synthetic compounds that were never really meant to be in the human diet.

And in the case of saccharin, for example, it was discovered by accident by a scientist in the late 1800s who was trying to make new coal tar for building roads. And he licked his fingers by accident at lunchtime and found this incredibly sweet substance that subsequently went on. He developed it as a saccharin. As the sugar substitute.

So we decided then to basically take a whole selection of these artificial sweeteners that are very common in the human diet and explore the impact that they have on bacteria. Because there’s been a huge amount of work exploring the impact that they have on humans and human cells, but very little in comparison then to the impact that they had on bacteria. So that was the initial starting point for this study.

IRA FLATOW: So were you surprised by this?

RONAN MCCARTHY: Massively. Massively. I still remember the day the student was doing the experiments in the lab. And she came down to my office and she showed me the data, and I was blown away because we had this sweetener, saccharin, that was essentially killing this multi-drug-resistant bacteria that traditionally is incredibly hard to kill with antibiotics.

So it was an incredibly exciting finding, one I almost didn’t believe to begin with. So I asked her to go back to the lab and do it five more times, and then we can have a conversation again. And she did it. And sure enough, the data held up. And it was a real nice starting point for this.

IRA FLATOW: So let me get this straight. So saccharin was able to kill bacteria that we currently don’t have effective antibiotics for?

RONAN MCCARTHY: Yeah, exactly. So we use a multi-drug-resistant clinical isolate of a bacteria called Acinetobacter baumannii, which is considered by the World Health Organization as one of the top priority pathogens because it has this incredible capacity to evolve and acquire resistance to antibiotics very, very quickly. And it makes it, then, incredibly difficult to treat. And yeah, then when we tested saccharin against this bacteria, it was able to kill it.

IRA FLATOW: What about stuff like MRSA?

RONAN MCCARTHY: Yeah, so very interestingly, the spectrum of activity for saccharin was really quite interesting as well because we showed that it was active against clinical isolates of E. coli, multi-drug-resistant Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter as I mentioned, and also Pseudomonas aeruginosa. So a real hit list of priority pathogens that are very, very problematic in a hospital setting in particular.

IRA FLATOW: Wow. So you have to tell me how saccharin does this. I mean, what unique properties does it have? How does it go about doing its deadly work?

RONAN MCCARTHY: Essentially, the cell envelope, which is the layer that coats the surface of bacteria and essentially holds all the content of the cell together– we saw that that was being weakened significantly. So much so that when we literally observed the cells under a microscope, they very quickly started to lose their traditional or normal shape. And then we would get these bulges in the membrane.

Now, anybody who’s ever driven a car, one of their car tires gets a bulge in the car tire, you immediately obviously have to take it to the mechanic to stop the tire bursting. Well, this is what was happening with these bacteria. They were getting these bulges, and all of a sudden, they would pop quite dramatically. It was fascinating to watch it on the microscope.

IRA FLATOW: Wow. So can you just then use saccharine itself and put it to treat a wound, let’s say?

RONAN MCCARTHY: So that’s the route we’re going. And we’ve developed wound dressings where we can have high concentrations of saccharine and put them on a wound. And one of the very, very exciting things we’ve observed with saccharine is with many of these multi-drug-resistant bacteria, they form these communities or these structures, particularly within wounds, but in many sites in the body called biofilms.

And these biofilms essentially encase the bacteria in a protective matrix composed of polysaccharides. And when the bacteria grow in these matrices, they’re incredibly difficult to treat because the antibiotic cannot get in to actually kill the bacteria. And there’s plenty of studies out there that show it’s between 10 to a thousand times more antibiotic you need to get the bacteria in a biofilm or to kill bacteria in a biofilm.

Now, what we saw with saccharin is that not only does it stop the bacteria forming these biofilms, but even if the bacteria has already formed one of these protective biofilms, saccharin can disrupt and dismantle that protective structure.

IRA FLATOW: No kidding. So have you actually created a wound dressing using saccharin?

RONAN MCCARTHY: Yeah. So we’ve created a wound hydrogel dressing. I suppose this is another barrier that commonly faces antimicrobials that are in development is that they work great when they’re purified. But when you put them into a wound dressing, for example, they lose an awful lot of their activity.

But we were really surprised and excited to see that when we integrated saccharin into a hydrogel wound dressing, that we were able to retain its activity, and it was still effective. So we’re currently– we’ve tested this in ex-vivo models where essentially we’ve taken pigskin, we’ve infected the pigskin, and then put the dressing on, and seen that actually the saccharine wound dressing works better than some of the antimicrobial commercial wound dressings that you can buy in your pharmacy.

IRA FLATOW: That’s amazing. So our listeners are all going to hear this, and they’re going to want to try this at home. Are you going to tell them, don’t try this at home?

RONAN MCCARTHY: Oh, Yeah. Absolutely. We’re still at the early stages of development for this. So this isn’t something you could try at home. The concentrations we’re using– and it’s very, very important to highlight this. The concentrations we’re using are not a concentration that anybody could possibly ingest. They would need to be drinking 500 cans of Diet Coke to get anywhere close.

But we’re very excited about how quickly we could maybe translate this into something you could potentially buy in your pharmacy, or that would be rolled out in hospitals. Part of the reason for this is the active ingredient that we’re working with here is saccharin, a compound that there’s a huge amount of human pharmacokinetic data out there about how the body responds to it.

So it should hopefully mean that it’s accelerated through the development pipeline much quicker than a brand new novel antimicrobial compound that there is no data on how the human body responds to it.

IRA FLATOW: All right. So the big picture– do you think this discovery could make a dent in the global antibiotic resistance crisis?

RONAN MCCARTHY: I absolutely do agree. One of the more exciting findings we’ve also found with saccharin is that it can make a bacteria sensitive to an antibiotic that it was previously resistant to. So I mentioned earlier that saccharin weakens the cell membrane. And what we’ve noticed is that allows more antibiotic into the cell.

And that’s a really exciting finding because, as we’ve mentioned and highlighted, so many of these bacteria are resistant to the antibiotics. And we need ways to make the antibiotics work better.

IRA FLATOW: Well, Dr. McCarthy, Thank you for sharing this really interesting research about saccharin with us.

RONAN MCCARTHY: Thank you very much for your time. Dr. Ronan McCarthy, Professor in Biomedical Sciences, Director of the Antimicrobial Innovation Center at Brunel University of London.

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