Instant Genius - Fungal infections, with Dr Rebecca Drummond

Episode Date: February 17, 2023

The World Health Organisation recently released a report stating that fungal infections currently kill around 2 million people a year and that they present a growing threat to human life. For anyone who has been watching HBO’s fungal zombie TV series The Last of US this may be cause for alarm. But how big is the threat of fungal infections, how well equipped are we to deal with them and could a fungus ever really turn us all into mindless zombies? We speak to Dr Rebecca Drummond, Associate Professor of Immunology and Immunotherapy, at the University of Birmingham. She tells us about the fascinating lifecycles of fungi, the threats they pose to human life and why we should be doing more to protect ourselves from them. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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delivering digital precision with analogue warmth. So you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. Hello and welcome to Instant Genius, a bite-sized masterclass in podcast form. I'm Jason Goodyear, commissioning editor at BBC Science Focus magazine. The World Health Organization recently released a report

stating that fungal infections currently kill around 2 million people a year and their threat to human life is growing. For anyone who's been watching HBO's The Last of Us, a hit TV series centered around a parasitic fungal infection that turns humans into crazed, flesh-hungry zombies, this may be caused for alarm. But how big is the threat of fungal infections? How well-equipped are we to deal with them?

And could have fungus ever really turn us into mindless zombies? We speak to Rebecca Drummond, Associate Professor of Immunology and Immunotherapy at the University of Birmingham. She tells us about the fascinating life cycles of fungi, the threats they post to human life, and why we should be doing more to protect ourselves from them. So first off, most of us are familiar with mushrooms. You know, we've all eaten them on pizzas or whatever. But let's start really with the basics. When we're talking about fungi, what's the strict scientific definition?

So fungi are their own kingdom. So they're completely separate to plants or bacteria animals. And I think that's some confusion that's often made, right? That they are somehow closely related to plants, for example. But actually, their closest relation is to us. So on this sort of tree of life, their closest relation. is animals. So they have very similar biochemistry to us. But they do have very distinctive features that make them very different to us. So for example, fungal cells have cell walls, which is similar to plant cells, for example. And then they have specific types of carbohydrates and other molecules that we don't have. So that's what makes them a bit different. And say they can exist in all different shapes and sizes. So you can start from microscopic yeast, which we would use to make, you know, beer or bread, and then they can make these very large complex structures like mushrooms that you

mentioned. And some of these can be massive. So actually, you know, we think one of the largest living things on earth is a fungus, right? So there's a huge fungus. They call it the humongous fungus out in the Blue Mountains in Oregon. I don't know if you've come across that, but it's pretty good. So yeah, so most of that's like underground. But when they've done genetic testing on it, they know that these mushrooms are all related, right? So I think it's one colony, which is several kilometres wide. So you mentioned there's a huge variation in the fungi kingdom. So do we have any clue how numerous and varied they actually are? We estimate somewhere in a region of about two million different species, but some estimates have put that up as high as five million, some have been a bit

lower. So we know that a lot of these fungi exist, but we don't know an awful lot about them, and that's partly because a lot of fungi, we just don't know how to grow in a lab, right? So we can do like, say, genetic testing of like a soil sample and we can look for pieces of DNA. And we can look for pieces of DNA that we tell us that fungi are there. But that piece of DNA doesn't necessarily tell you anything about what carbon sources that fungus likes or what temperature it likes to grow at. We can make some educated guesses based on where we found it, but that doesn't necessarily translate into growing it in a lab. So we know there's a huge diversity of fungi out there, but the true diversity, we still don't really know. So what makes them so difficult to grow then?

Because you often see, you know, you get wild mushrooms are very popular in restaurants and things, So people say they're incredibly difficult to farm, even though that would be a really lucrative business if you actually could. What makes them so difficult to farm or to grow? I mean, I think one thing we need to remember about fungi is that they are shapeshifters. So although we see these mushrooms, it doesn't mean that it started off its life as a mushroom, right? So usually what happens is, I mean, most fungi will produce spores and it'll make these airborne. And then those spores will then go on to, you know, germinate and form a new type of cell, usually something like a, like a, like a mycelium, right? So a sort of long, thin type of cell. And then these can then make

networks and then eventually you can get these fruiting broadies, which are called, you know, which look like mushrooms. But in order to make the spores, and often what you need are the different fungal cells have to undergo sexual reproduction. And that's a process that's actually really quite complicated because it involves, you know, sort of genetic mixing and things like that. You usually need fungal cells of different genetic types in order for that process to happen. The environmental conditions are also quite important for this as well. And that's something that's very difficult to replicate in a lab. And so that can be one of the reasons why it's quite difficult to grow, because you're not only just trying to get the particular fungal species that

you're interested in to grow, but you're also trying to get them to shape-shift into the shape that you really want. And so that's what can make them quite hard to grow. But that's not true of all species, of course. There are some fungus that just seem to pop up everywhere like the molds. Yeah, so you mentioned that they're sort of deeply embedded in their environments. So what sort of role do they play in the various ecosystems that they live in? I mean, fungi are sort of typically considered the decomposers, right? So they're really important for our environment in terms of getting rid of things like dead animals or dead plants matter and things like that. So they're really important. That's where we often see mushrooms, right, around decaying trees and things like that. So yeah, so they're really important from that perspective. But they're also found in other surprising places as well. So I think there's been a lot of talk of the last few years about our microbiome, right, and having good bacteria and bad bacteria. But fungi are also a really important part of our microbiome as well. So you have a lot of yeast species that actually reside in your gut. And so that's another place which we can find them.

And there have been some studies to suggest that these fungi might also be important for, you know, our gut health or keeping us healthy, but potentially also predisposing us to different diseases as well. So this is still an area that we still don't really understand an awful lot about and something that we're trying to understand more. Yeah, so going back to something that you mentioned earlier, that they're actually closer to animals than they are to plants. So you often hear a sort of pop culture stat thrown around that humans share something like, I might be wrong, it's something like 50% of our DNA with fungi. So what does that actually mean? In practical terms, what it means is it's really, really difficult to make antifungal drugs. So we actually have very limited numbers of antifungal drugs. So when fungi start causing infections,

it's hard for us to get rid of them. So we actually have a handful of antifungal drugs available to treat you, you know, if you were to come to hospital with them. And the reason for that is, as I mentioned, because they're so closely related, their biochemistry is very similar to ours. So if you're trying to make a drug that's going to be toxic to the fungus to actually, you know, cause it to die, you have to make sure you're targeting some kind of biochemical process in the fungus that's not going to target the same biochemical process in our cells. And that's what's led as to being quite hard to develop these different antifungal drugs. And so that's why we're much more limited there than we're are in comparison to antibiotics, for example, where we have hundreds of different types.

Yeah, so let's move on to this recent World Health Organization report then that recently said fungus is a growing threat to human life. Something like, I think it said, two million people a year die from fungal infections. Is this really a legitimate concern? Yes, absolutely. So I think we have been ignoring fungal infections for a very long time. and so it was really pleasing to see the World Health Organization actually making a point of this problem that we're having. Part of the reason for that is that fungal infections are not really natural infections of humans. Actually, as humans, we're quite resistant to fungal infections. Our immune systems are really, really good at fighting these fungi.

The problem comes in when your immune system becomes damaged. So if you have some kind of component of your immune system missing, or there are various different drugs. Actually, I mentioned antibiotics. antibiotics can do this as well. They can damage our immune system in such a way that this creates holes in our immune defences and then fungi can get in and cause problems. Now, what's happened over the last sort of half century or so, people who have damaged immune systems have increased. So that population has massively expanded. So to give you an example, the AIDS pandemic would be a good one, right? So you have lots of people who have now living with HIV. They are now very susceptible to getting

various different fungal infections. Lots of cancers as well. So we, we, give a lot of drugs to treat cancers, but these drugs have the side effect that they can damage our immune system. And as a result, we see fungal infections popping up in various cancer patients as well. And so that's why fungal infections are really problematic right now, because we're dealing with a group of patients who are very difficult to treat and very clinically complex. And as I said, we're limited in our antifungal drugs and on top of that as well. And so that's why it's really important to we try and understand a bit more about how fungal infections cause disease, how the immune system, what is the damage in the immune system that actually leads to

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and unforgettable listening experiences at home. Try it for yourself at a focal powered by name boutique. Visit focal powered by name.com for more information. So what are some common fungal infections then, you know, that perhaps our listeners may have heard of? It's probably the most common one that everyone will have heard of is thrush, right? So this is caused by a yeast called candida. So there's a lot of different species of candida. But this is sometimes known as like the white fungus. So it's a yeast and when it

grows in the lab, it grows in the very white colour. And this is one actually that's part of your microbiome. So most of us actually have it in our gut. But say there are certain things that can cause damage to the immune system that this fungus can then start causing infections. So a common one is antibiotics. So if you take antibiotics for a long time or you have several courses of these, then these infections can come up. And so when it causes infections either on your gums or on your tongue or in the vagina, then we call this thrush. So that's a really, really common infections.

We think billions of people around the world get thrush infections every year. But it can also become very dangerous. So this is when it becomes invasive candidiasis. So that's when the yeast gets into your bloodstream and invades into the different organs like the kidney and the liver. And that can cause multi-organ failure. So that's a much rarer form of the infection, but it's still pretty common, as I said, people who have, you know, severely damaged immune systems. So that's probably one of the more common ones in the UK. Another common one that we see in the UK is aspergillosis.

So this is a mold infection in the lung. So again, this tends to affect people who have various lung problems like cystic fibrosis, you know, lung transplant patients. They can be quite susceptible to this type of infection as well. So that's particularly common in the UK in terms of deans. dangerous fungal infections. And then probably the biggest killer of humans from a fungal infection is a disease called cryptococcal meningitis. So that's a really big problem for people who have HIV, particularly end stage towards AIDS. So cryptoccal meningitis kills, we think, around 100,000 people every year, mostly in sub-Saharan Africa where the burden of HIV is at the highest,

but also where the access to various antifungal drugs is a bit more limited there. as well. So these are the sort of, I would say, the three big killers. Yeah, so you mentioned earlier that the kingdom, the fungi kingdom, is incredibly varied. I mean, does that cross over to the infections, the infections equally varied? I guess it depends on who you ask and how you look at it. So I think one of the traits that all of these fungi share that cause infections is that he can actually grow our body temperature. So the vast majority of fungi can't do that. So as I said, there's millions of different species, but actually only a handful will cause human infections, right? And that's partly because they all share this trait that they can grow at 37 degrees Celsius.

So they're all sort of similar in that respect. Most of the fungi that will cause infections in humans are not from the mushroom sort of family. Fungy exists in these sort of group fungi into two main families. So there's the asco mycota and the basidio mycota. So most fungi that cause infections are in that ASCO mycota family, and that includes your yeasts like your brewer's yeast, but also the candida and the aspergillus that I mentioned that cause infections in humans. And most of your mushrooms are found in the other one, the basidio mycotta.

And there's only really one sort of fungal pathogen that we find within that. And that's the cryptoccus fungi, which caused the meningitis and AIDS patients. So I would say that most pathogens are mostly more closely rated because they're in the ascomicota, but not necessarily. So there are exceptions to that rule. And even within the ascomicota, they can still be quite genetically distinct. So in evolutionary terms, they're still very far apart. But they do share certain traits which allow them to cause infections,

such as being able to grow at our body temperature of 37 degrees Celsius, because that's an unusual trait amongst the fungal kingdom as a whole. Yeah, so you mentioned earlier the difficulty with developing drugs to treat fungal infections. So how do we currently go about developing drugs for these infections? So there's a couple of approaches. One is that we can actually still look for new targets. So there's still a lot about fungal biology that we don't understand. You know, I mentioned how with so many fungi we don't know how to grow. And then for the, you know, the ones that cause

infections, there's still a lot about their biology we don't understand. So there's a lot of groups trying to understand that biology because if you can understand, you know, for example, how that fungus responds to stress, like, you know, oxidative stress. So, you know, like we talk about, you know, oxygen radicals and things like that that can be made by our immune system. If you can understand how the fungus is trying to defend itself against those defenses, then maybe we could design a drug to kind of counteract that defense of the fungus. So that is one approach. And then one approach, which is one that my lab favors because we're an immunology lab, is to try and do immune boosting drugs. So finding, I'm trying to understand what is the immune

system needs to fight a fungal infection. Because if you can understand that, then maybe you can then replace what's missing in your patient who's getting the fungal infection. So we can do this by treating with maybe cell types of transfers. So people have done these types of experimental treatments with cancer, for example. But you can also treat with molecules called cytokines. So these are like little signaling proteins that we use that activate immune responses. So we try to understand how those work in the context of a fungal infection so that you can try and potentially use that as a strategy. And I think in reality, what you'd end up doing is a combination of both. So you would have a patient who you give an antifungal drug to try and slow the growth of

the fungus. But you would also give them a drug that could help boost the immune response at the same time. and in that way, try and treat your patient against the fungal infection. Yeah, so how do we, how do fungal infections spread? How do we get them and can you pass them on to other people? So we mostly get fungal infections from breathing in their spores. So most fungal spores are airborne. So we breathe them in all the time. And as I said, if you've got a nice healthy immune system,

actually you're being exposed constantly. You're breathing them in every single time you go outside. It's only when the immune system is damaged that that spore might not get destroyed by the immune system. and it might germinate inside your lung, and then the fungus can then shape shift into a yeast or one of these mycelium or something like that. And that's when you can get the infection. There's not much evidence to suggest that once the fungus shapeshifts from a spore into another cell type in your lung, that it would go back into spores. So it's not like we're breathing out spores, and then we would infect other people. So there's not much evidence that fungi are infectious diseases in that sense.

So it's not like a virus where if you're near an infected person, you might kind of. hatch it. So fungal infections typically don't spread like that. You tend to get your fungal infection from the environment instead. Okay, so sort of jumping off from that, so we're talking about fungal infections. So one thing that a lot of people are talking about at the moment is the TV show, The Last of Us, which is the central premise is that the human race is infected with a fungus that turns them into, I don't know, violent zombies, I suppose you could call them. And in the series, the fungus that causes the problem is it is a cordyceps. So this is actually a real fungus,

isn't it? Yes, that's right. So again, this is a large group of species known as the cordyceps fungi. They mostly infect insects, and then within that, there's even smaller number of the cordyceps fungi that when they infect insects, they actually seem to be able to exert some kind of mind control. So they'll infect the nervous system of the insect and control the insects movements. These cordyceps fungi are very well adapted to their hosts, so you'll of one type of cordyceps that will infect an ant, say, and another one that will affect a grasshopper, one that will infect a spider and so on.

So they're very, you know, kind of specific to their different hosts. Yeah, that's where we see a lot of similarities with the TV show, and what we see when the insect becomes infected, they start to move kind of against their will. And usually what's happening is the fungus is trying to force the ant or the insect to a site where the fungus can germinate and release more spores, and thus it's spreading the infection that way. way. But there's no evidence that cordyceps have currently infects humans. So how does it actually,

what happens then when it takes over the host? Does the, the insects, it entails the spores and they grow inside it, something like that? Yeah, so there's some evidence suggests that the fungus actually seems to almost go into sort of like the musculature and the nervous system of the ant, and we think that that then helps control how the ant is then going to move. I think exactly how that works is not particularly well understood because while we don't understand an awful lot about immunity to fungal infections in humans, I think there's even less

known about that in insects as well so there's still a lot of being unanswered questions there about exactly how that works. So the cordyceps is having an effect on the insect. Does this have anything in common with say like psilocybin mushrooms and things like that

which obviously have a potent effect on human brains? I think that's a really good question and not one I think anyone's really tried to answer yet actually. I think those fungi are quite divergent so I don't know if it would be exactly the same effects, but it's an interesting question, but it's one I'm afraid I can't answer because we've not looked. Are there any fungal infections that can spread to the human brain? Yes, so a lot of them can actually. So as I said, I mentioned earlier about cryptococcal meningitis. So that's a fungus. Again, we inhale the spores to get into our lung and it can cause a pneumonia.

type of disease in the lung. But actually when most patients present is when it's already in the brain. So it gets out of the lung, the fungus gets out of the lung and into the brain. And we don't quite understand how that happens. We think what probably happens is that the lung gets damaged and maybe you get some bleeding. The fungus gets into the blood and then it can traffic its way up into the brain. And once it's in the brain, it causes significant problems there, as you can imagine. So a lot of the symptoms you see are kind of typical symptoms of meningitis. You know, you might have vision loss, seizures, you know, memory problems, that type of thing. And it can cause very significant damage. So even people who survive that infection are often left

very, you know, with neurological impairments as well. But the other fungi that I mentioned, like the candida yeasts, the aspergillus, they've also can cause significant brain infections in humans, although with those ones, that tends to only happen in patients who have been left untreated for one reason or another. So if you let the infection run its natural course, most of them will end up in the brain. And that's usually the most lethal form of the infection. So that's the most dangerous and the most difficult one to treat. So in the show The Last of Us, the way that they get around the fact that the, as you mentioned earlier,

the 37 degree temperature of the human body isn't suitable for a suitable environment for cordyceps, for example, in the show to live in. They get around this by saying that actually they've adapted to increase temperatures that have also due to climate change, and that's allowed them to make the jump from insects to human hosts. Obviously, that's probably a bit of a jump, but is there any reality in that idea? So there is some reality in that idea, and there are actually some examples where we think fungi have adapted to warming global temperatures. So not cordyceps, which might put some people at ease, but there are some other fungi that are causing is quite a big concern. So I mentioned

the candidacy species, and there's a particular. species of candida yeast called Canada oris. Now that we had never really heard of that before 2009. So it was a kind of, it's a fairly new emerging species of this yeast. And the reason that we're very concerned about it is because it is adapted to grow at much warmer temperatures. So in a lab, for example, you can grow up right up to 42 degrees Celsius. And that's very unusual for a fungus. And it can cause infections in people who have defective immune responses. One of the reasons that we are particularly concerned about it is since 2009, it's appeared in three different continents. And they also appear to have, we seem to have detected it needs

to continents almost simultaneously. And when they've done genetic testing on say Canada oras from Europe versus North America, what we find is actually they're genetically distinct. So it's not as if it was first discovered in Asia and it's just moved your spread around the world. It actually seems to have independently picked up this trait in different locations around the world. And that's kind of weird, right? So it's still very much a theory. But based on some of the research that we're doing right now, that does seem to be a viable theory that the global warming temperatures is actually given rise to this fungus called Candidorus. And the other major concern we have about that fungus is it's inherently resistant to many of our antifungal drugs. So it's sometimes referred to as the first fungal superbug because we have very, very limited ways of treating that particular infection.

So that's a particularly big concern for a lot of healthcare, you know, like the CDC, for example. are watching this closely. Yeah, I mean, not to be alarmist, but is it possible that a previously undiscovered fungus could come to light that presents a threat to human life? I think so, yeah. So there are some other species

that have only really been described in the last couple of decades, if that, that we really didn't know anything about, but have started to cause infection, particularly in Africa, for example. So there's various countries there that have been reporting another fungus that, again, we had not really heard

very much about at all until quite recently. So yeah, I think it is a concern. It's something that we definitely need to be paying more attention to, but our surveillance that we do for fungal infections is much more limited compared to, say, bacterial or viral infections. So a lot of these fungal infections that I've mentioned are not reportable. So there's a lot of hospitals, for example, that would not report that they've had a person who has died from that infection. And that makes it very difficult for us to understand how big the problem really is. So there's a lot of campaigns now to try and make sure that we change that. So we can think a lot more about how to figure out how big a problem is the fungal diseases and which fungal species are the biggest problem that we need to be worried about.

So there's not like a sort of international protocol in effect whereby scientists keep track of any potentially emerging threats or things like that or even the picture as a whole? No, no. So there are some research groups out there that are trying their best with the data that they have and they're, you know, publishing reports to try and put that data out there. But it really is the effort of a small number of people. There's no concerted effort to monitor all fungal fictions as a whole. So yeah, that does make it very difficult for us to understand where or how policy might need to change in different countries, for example, to best tackle this problem. Yeah, another thing that I found from watching the TV show that I think a lot of people would be

interested in is the network of fungi seem to be able to communicate with one another. And I've, I've read some studies saying that this type of thing, you know, is this something that they're actually able to do? Yes. I mean, I think a lot of the sort of environmental fungi, particularly ones that grow, you know, like saying forests and things like that, they can make these vast networks and use that to communicate with one another. So as I mentioned, these kind of like mycelium type cells, you know, these can grow and merge into one another and almost create highways, which they can use to pass information and say these can become very, very large, right? So we sort of talked about that humongous fungus in Oregon. That can be a good example of how you have this huge

network where presumably there is a lot of communication happening between those mushrooms at different sites. That was the University of Birmingham's Rebecca Drummond. Thank you for listening to this episode of Instant Genius. Brought you from the team behind BBC Science Focus magazine. The current issue of BBC Science Focus is out now. Pick up a copy. wherever you buy your favourite magazines or download a digital copy from your preferred app store. You can, of course, also find us online at sciencefocus.com. This podcast is sponsored by Name, Audio and Focal. The texture and emotional depth of music can be lost through digital sources or poor signal.

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