Infectious Fungi - Dr. Neil Gow

Transcribed by https://otter.ai ** Subject to error

Alex 0:00
You're listening to the mushroom revival podcast.

Lera 0:04
Today on the show we're talking with mycologist Neil Gao who has formal training in mycology, especially in relation to human and fungal pathogens. Despite his research on combating fungal infections Neo is a big time myco file with loads of great information on this impressive Kingdom of life. We discussed the pervasiveness of fungal infections, which fungi are most likely to cause zombie humans, injecting psilocybin spores into your bloodstream, mechanisms of pathogenic fungi and so much more.

Alex 0:37
Some early content for spooky season for you but before we dive in a note from our sponsors, us if you like the show and you want it to go on, you can help us by supporting us. How do you do that? Well, you can visit our website at mushroom revival, calm and purchase any of our products to support your energy focus, calm immune system and your defense against occasional stress all with the power of functional mushrooms these beautiful beautiful organisms. podcast listeners get a special surprise discount just enter ----- at checkout to see what that surprises we're not going to tell you how much of a discount you're gonna get. But you got to find that out yourself. Think of it as an Easter egg so that's ----- at checkout. You can also support us by rating and reviewing it means seriously the world to us when we see reviews come in and people spreading the mushroom love and just it really means the world to us and it gets you featured on our show because we select a review every week and this week is from n m f dash s Mashallah love, quote unquote love learning from you both and your guests. You both asked such great questions and explain things on a deeper level. I love to listen in the mornings and start my day with inspirational spores that end up floating through my head all day. Cheers smiley face. And m f dash s. Thank you so much. We'd love to think about spores floating through your head, although we hope it's not cryptococcus more than that. In today's show.

Lera 2:36
Neil Gow, thank you for joining Alex Nye on the mushroom revival podcast. To talk about your specialties in the field. Would you start by telling us who you are and how you took an interest in mycology?

Neil 2:50
Certainly Lera Yeah, it's great to be here. I suppose I'm a professional mycologist I've done a variety of types of mycology, I've worked in a university research environment my entire career. I'm currently at the University of Exeter, which is in the southwest of England. And I hold the position of being Deputy Vice Chancellor, which is in charge of their search program, the university but I still have my own lab. And my own speciality is in funghi, which cause serious diseases and people so that's the field of medical mycology.

Alex 3:26
And I'm curious what was your academic training like and and how many subjects Did you did you need to learn that that weren't specific to mycology that helped create a well rounded education and what do you think was lacking? What do you feel like there was enough mycology education or do you feel like it can improve significantly?

Neil 3:51
Oh, my college is an odd discipline. In that sense, it's part of the umbrella under the umbrella of microbiology. But a lot of my colleges grew up and have training in botany, which I did not. I had training in in mycology actually started off in molecular and cell biology and zoology, but trained in medical mycology from my PhD onwards, but I've worked in a whole range of different funghi during that time and come to love the funghi as a kingdom as a whole. And I also do quite a bit of immunology. But the mycology world is quite a small one compared with a very large size of the world and that studies microbes as a whole, and medical mycology is only a very small part of the field of infectious disease biology. And in fact, that's one of the problems of medical mycology, even though it's a really important part of international health care which we can talk about on Typically about two to 3% of funding and infectious disease biology goes to people studying fungal diseases. But that does not reflect in any way, the real scale of fungal infections, which is a massive world problem.

Lera 5:15
Really, do you know what that's gonna look like?

Neil 5:18
Well, I always tell people and scales fall from their eyes when they realize that there are far more people die of fungal infections than for example, malaria. And an approximately equal number of people die of fungal infections that die from now from HIV, and even tuberculosis. These are all diseases that everybody every reasonably educated person knows quite a bit about. And almost nobody would appreciate that fungal infections have that type of burden. And in fact, if you look at things, organizations like the world, World Health Organization, that who they list fungal infections as the third most common human ailment, and after things like backache, because things like skin infections, in fact, about a quarter of the world's population, there are actually more people who die each year of fungal infection then of breast cancer or prostate cancer, for example. So it's really a highly under appreciated discipline. And unfortunately, that means that there's not the size of community to study these diseases that that serious set of diseases deserves.

Alex 6:30
You should have seen both of our faces were in extreme placement. I mean, it, I would never have guessed that. Do you have a specific number of you know, estimated annual deaths? And is this a wide range of fungal infection? is there is there one particular fungal infection that's more dominant than the others and more of a killer?

Neil 6:52
Well, I could start with the overall numbers. And actually, that is quite difficult to give you with any degree of precision, because many of these diseases and those people who succumb to fungal diseases do so in developing countries around the world, and so it's very under appreciated here. But that's not to say that you couldn't be at risk from a serious fungal infection in the West, you are. And the numbers look like sort of estimates. And these are sort of ballpark figures. There's about in terms of skin infections, more than a billion, so probably near 2 billion. So let's see roughly a quarter of the world's population in terms of serious infections of the mucosal surfaces, which includes lung infections and allergies, etc. We're talking hundreds of millions of dollars of infections per year, in terms of attributable deaths due to fungal infections, that number is, I'll get my best number would be about one and a half million people die a year. And that will be in contrast as sort of like half a million people dying of malaria, which I gave you as a kind of more familiar benchmark. So these are really, very large numbers of people were affected. And the health burden of treating people who are susceptible and in danger of succumbing to a fungal infection is enormous. So for example, people who are recovering from seed treatments for cancer often have very low immunity. And they're exquisitely open to potential infections due to funghi. And it may cost two to $5,000 a day to protect them from fungal infections. So there's a very substantial health burden and financial burden. And the era of COVID, as well has generated all C's of new infections, which are extraordinarily difficult to budge, difficult to treat, and very serious and exacerbate the problem due to COVID.

Lera 9:00
So I sign up for Google alerts for any news that comes out with the word fungus, fungi, mushroom, etc. and overwhelmingly for the fungus one, I was getting alerts for this black fungus outbreak mostly in India. I haven't heard it in Western media whatsoever. What is up with this? And additionally, if you could kind of define the specific fungal infections that the human population is so susceptible to, I mean, is that there's an overwhelming type of infection that people are dying from, or is it just a medley? Yeah.

Neil 9:38
Let me let me deal with that second question, then go back to your COVID question, because that's a different situation. Actually. There are, as you know, only too well, very large numbers of funghi. And in fact, they're only eclipsed by the insects in terms of biodiversity, that we don't even know how many fine There are those there's certainly in the region of 5 million species. But the numbers which cause human infection are a tiny subset of that are very tiny. And in fact, there's only about three or four genera, major groups of funghi, which are serious infections and the general which includes encompass by Candida, Aspergillus and cryptococcus and pneumocystis. Those four would account for roughly 95% of all attributable deaths. Now COVID opens the door to other things, but you do get COVID Association infections in those groups. So there's something called Kappa COVID associated pulmonary aspergillosis, meaning that people who've got lung infections have got a double whammy, often because they become susceptible to fungal infections as well, as happens with influenza. And in fact, in some places around the world, such as in the Netherlands, people will treat prophylactically against Aspergillus because it improves your ability to to recover from serious influenza infection. Now, you mentioned black funghi from India. So in India, we've there's a very large number of people dying of fungal infections caused by a fungus called mucor. And the disease's called mucor, mycoses for mucor, fungal infection, about 9000, estimated in a year, whereas typically pre COVID, that might have been two or 300. And you get a few 100 in the US and in Europe, but it's very uncommon. So it is become much, much worse due to COVID. It's called Black use is a bit of a misnomer, actually, because there are black funghi, which are black, they have got the dark pigment melanin in them. And muker generally doesn't it certainly doesn't when it's growing in the human body is called Black, unfortunately, because the tissue turns black because of the light the loss of the blood vessels and blood supply to those tissues. And it's a very serious and horrendous disease, often requiring surgical debridement. That's removal of tissue by surgery, and long term antifungal therapies. And even then, the success rates of treating mucormycosis this black fungus is actually very poor. And some of these fungal infections which caused these deep seated hidden infections, the recovery rate might be much worse than 50%. Some cases 90% of people won't make it. So these are really horrendous diseases, which we don't know enough about. We don't have the right armamentarium of antibiotics, antifungal drugs to treat with. And there are real limitations.

Lera 12:47
So we have a lot of questions about like the mycology of why these things are so tough on the human body. But before we dive into there, I kind of want to have a scope of fungal infections. So in the Western world where most of our listeners are, they're probably familiar with things like dandruff and ringworm and like athlete's foot, are there any other common ailments that aren't necessarily serious? But you know what, maybe people don't know our fungus, like when I found out that dandruff was caused by fungi, I was like, Whoa, yeah, you

Neil 13:21
know, it is and that those people who've got Mac gun dandruff are not even included in those who figure. So it's probably that virtually the entire population is suffering for it to some extent for is infected and colonized by the group of funghi, which cause dandruff, and they've got the ability to grow in the oily skin. That's basically what they do. But one thing which I have not yet mentioned, is that thrush is also a fungal infection, and 100 million women, that's 100 million suffer from four or more recurrent episodes per year. Now, that might not be a life threatening condition. But that's a miserable sentence. And we don't know enough about why some women are particularly prone to recurrent infection due to Candida, which causes thrush. And some women don't have that. You'll be shocked. Certainly many people are very surprised to know in the age where we're thinking a lot about vaccines for COVID. And what a difference they have made is there is not one single vaccine that you could go to in any part of the world to protect you from any of the funghi I've been talking about. There is one in development in the US against recurrent thrush infections, which is giving us some hope for the future. There's no reason per se why we shouldn't have vaccines against fungi, but we don't have any at all of yet. So we treat we treat the infection, we don't generally do so much to protect us from getting the infection in the first place.

Lera 15:10
Do you think the lack of a vaccine is just due to lack of funding and research? Or is it because fungi are more tough to kind of vaccinate against compared to viruses or bacteria?

Neil 15:23
It's a very good question allows me to reminds me to say something very important about these fungal infections. And that is in terms of life threatening affection. These are extremely rare in people who have full a normal healthy immunity. those diseases tend to be the disease of the disease of people who've got some under lying precondition, which makes them vulnerable. And then they become open to this. I mentioned cancer patients, for example, and other forms of immune suppression. So the sort of funghi, which cause disease mostly, and that's not obviously the case for things like ringworm, which can affect anybody. But often the effects somebody where there is an alteration in the ability to, to protect ourselves from funghi. Because Bungie have been around since the dawn of time, really, in terms of, they've been part of the microbiota of the world for a very long time, literally more than a billion years, maybe a billion and a half years. And during that time, mammals and humans are late developing animals have spent a lot of time developing systems to fend themselves against funghi. So we've actually got quite sophisticated immune systems, which are rather good at looking after funghi. And in fact, there are more recognition mechanisms to detect funghi in the immune system than probably for any other type of infectious organism. So however, that breaks down quite commonly, there's a lot of people who don't have normal immunity. And it happens to some people for part of their life, you know, if they have an illness, for example. It could be a transitory thing, or it could be a permanent thing if you've got a genetic predisposition, and all of these factors that ultimately are important and relevant.

Lera 17:21
So of the fungal infections that really infiltrate society, are most of those yeast like.

Neil 17:31
So there's a variety, there are both yeast like pathogens like Candida, and cryptococcus, is another example of that. cryptococcus is an infection of the central nervous system and brain gets in there. So it It causes meningitis. And when most people think of meningitis, they're thinking of viral or bacterial meningitis. But actually there are very large numbers of people get fungal meningitis, yeast, like infections, they include Candida, but there are filamentous organisms. muker, which you've mentioned, is one. And Aspergillus is another. So there's a variety of different organisms which can cause human disease. Some of them actually are quite notably, ones which switch their shape. So a lot of the organisms which cause human disease are some of them have one shape when they grow in the environment, you know, and on a leaf surface, or on some cases, bat dung, guano, other sorts of things outside the human body, but once they go inside the human body, they change their shape. And so many organisms, which are, for example, yes, it the environment, change and can become more filamentous can that can be can change shape and become more filamentous in the body. And others will do the reverse. They'll actually be filaments from the environment, and then switch to being used in the human body. And that's interesting, as well as

Lera 19:03
I'm interested to get your perspective on a case study that happened many years ago now. But this person injected himself with mushroom tea that he made. And I read part of the case study, but it seemed like possibly spores from these psilocybin mushrooms he injected into himself, got through this cotton ball that he used to filter it, and started germinating in his bloodstream and made him super super sick. Did you hear about this? And like, yeah, yeah, what can you say? It's someone who actually knows their mycology. First of all,

Neil 19:41
don't do it. Don't do things like that. That is crazy. It's very unfortunate. This this poor individual who was I think he suffered from bipolar disease and he had heard, which is there is a serious area of research investigating The fact that these hallucinogenic mushrooms including psilocybin, cubensis, which is the the fungus that he made a T spore cocktail out of and then injected, that these hallucinogenic mushroom when when you get this they can be have a positive effect on people who suffer from depressive illness that is thought, although this is very much a non regulated area where there are a lot more research needs to be done. But some of you may have seen the film fantastic funghi, which, which deals with us anyway, this person did this, it was a poor thing to be able to do, because you're when you inject something into the bloodstream, you're immediately bypassing a lot of protective barriers, which keep us clean and free from fungal infections, which are out in the yard. And in the, in the environment of the place. mercifully, this guy, I believe, did recover. He was about three weeks in hospital, I believe. And he recovered, because eventually this would kick in but and the disease which could which he had might have been a head systemic organ failure of a number of organs that might not have just been due to the fungus growing. In fact, I'm not even sure that the fungus would have grown inside the body. But you can get disease from funghi very commonly without growing because they can induce very strong inflammatory responses and cause a sort of storm of inflammation, which some people will have heard of in, in respect to, for example, COVID, which is another example of that influenza, there are many diseases which are caused by inflammation, I suspect that that might be part of the pathology that this person actually had. And that, and I suspect that because I think most environmental funghi are mentioned only a tiny number, actually are commonly recognized as causing disease. And that's because most of them can't grow very well at all, at 37 degrees, body temperature, and I suspect this, this fungus would have struggled to do that. But if you put enough in there, you're adding something very different the bloodstream, which is recognized as foreign, and your inflammatory response would be hyper activated, which would not be not be good. And we'd have all sorts of systemic problems for doctor to treat.

Alex 22:32
So we used to have a pretty large quarter sets militaris mushroom farm in the East Coast of the US, and we used to get all these mushroom newbies commenting on our posts on social media being really scared that, you know, we were going to take over the world and infect the human race with these gorgeous apps. And they thought, you know, this was straight out of a sci fi movie. And, you know, I'm obviously they're not that invested in mycology, and there's other mushrooms that will grow inside of the human body like schizo philam. And, and all the fungi were we've just been talking about. I'm curious if there was a fungal apocalypse that attack the human race. If that was ever possible, what fungi Do you think could be capable? And do you think you would be the most scared of

Neil 23:32
Alex Great question, transcending science fiction and fiction and science? Have you read the book? The genius plague, by the way? No, I haven't. Alright, there's something for everybody to have a look at. Because it has anticipated exactly what you've just said there and turned it into a novel, which I think it was a science fiction novel of the year a few years ago. Oh, wow. And it's based on this idea that people were tribal people in Brazil, became infected with psilocybin and the, this entered the brain and caused neural circuits to be reinforced, causing them become super intelligent. That's the premise of the book.

Alex 24:14
That's the best fungal infection to get.

Neil 24:17
It's, it's it's actually quite an interesting read. But quadriceps is a very, very interesting organism. And you'll, you know, this well and and probably broadcast are both here, but it does have effects on the behavior of insects when they infect them, causing them often to claw to the tops of trees, where they can then infect the body and then spoil it's inside their body. And the spores be now at the tops of the trees can be disseminated over very wide distances. So they're sometimes called, they can cause things like zombie ant syndrome because the ant is no longer in control of its own behavior. Now sillas the quadriceps is not an organism that's ever been associated with an infection and is highly unlikely to be able to grow in the break in the human body, let alone in the brain. Having said that, I did tell you already that cryptococcus there are several several species of cryptococcus can cause meningitis and does grow in there. And they don't, they cause very serious infections. Indeed, as you could imagine, because they cause enormous pressure to be developed inside the central nervous system, which is also an immunologically protected site, which is very difficult to deal with. So that is a very frightening organism. And it accounts for it's very difficult to estimate how many people die a year, but probably the most conservative number system might be a couple of 100,000 deaths a year, some have increased that number by a factor of more than five, but I think the best numbers are somewhere around a couple of 100,000 of people infected with that organism, in in particularly in Sub Saharan Africa is a terrible, terrible curse. And it's also got an organism which has got a capsule roundabout at a big gloopy, gelatinous, sort of shell round about it, which again, makes it very difficult for our blood cells to to grab ahold of it. And it can do other things, which makes it even more difficult it can grow, it can tighten eyes, they say there are people discovered that its ability to become Titanic sales Titan, meaning very large sales, which are more than 10 times the normal size. So big, they're completely indigestible to the phagocytes that normally would swallow them up in the immune system, and they become even more difficult to get rid of. So I think that is a horrendous curse. It's a very poor prognosis. Still, there are an adequate methodologies for this are there are some new, mercifully, some new advances being made both in diagnostics and in treatment for that organism. And it did actually emerge also in Canada as an outbreak in Vancouver, and in British Columbia a few years ago as a related species. So and that was in people who were not very immunosuppressed. So that was quite a fright. So that's a particularly what a worrisome organism. And there are other organisms which cause necrotizing disease, such as mucor. I think those are amongst the most, you know, disturbingly difficult organisms to treat with extremely difficult pathologies. So I put cryptococcus and mucor, up there amongst the kind of the House of Horrors group of organisms which cause fungal infection.

Alex 27:57
And I'm just reading about three specifically for cryptococcus. There's three major antibiotics that are routinely used. Are these only partially effective and have a partial success rate? And is that or are they generally infecting people in more rural areas where they don't have access to these antibiotics? And so it's more dangerous for those individuals.

Neil 28:28
So you're touching in a very big and important area? Now, everything you've said, is part of the answer. There is no or very few antifungal drugs, which some of them are antibiotics means that they're natural products produced by other organisms. But there are a few of these antifungals, which have got the broad spectrum of activity that we see with see the beta lactams, including the penicillin groups, right. So some are effective against some groups. Some are not effective against those some groups, some cryptococcus, you mentioned in particular, that's often successfully treated with a combination of drugs, which is more complicated to administer, and requires additional legislation. And then you also mentioned whether the availability was there. And that's important because antifungal drugs are by and large, expensive. So and, and some of them which would be very useful for cryptococcus have not been licensed around all of the African countries, for example, which require them. People are working very hard to try and change that. But the fact is, at the moment, we're still in the situation where they're not often available. And there's also another problem, which is increasingly important to address which is that drives Resistance is becoming year by year a more problematic area. And we're seeing the emergence of new fungus such as one very well known now called Candida Oris. Or a Stan is for oral as an ear so it was originally isolated as an ear infection but Candida Oris is a multi drug resistant organism most ora strains are resistant to easels and he is also the most common choice of drug to treat medically important funky with is also work pretty well against Candida albicans. And other Candida species by and large, but they are more strains are resistant, resistant or insensitive in terms of Oris. And the you said there are three groups there. Right, so easels was the first, a second one is a drug which is attacks a fungal cell wall ukraina candon. So several classes of that. And then there are also a set of drugs called paulines, and polyenes attack the membranes of funghi. What they tend to do is interact with the fungal stearoyl, which is different from our steel orals, we have cholesterol, and many of you will have had to have been tested for your cholesterol levels. funghi have got a related compound called ergosterol. And luckily, ergosterol and cholesterol are different enough from another that you can target either the synthesis of our gospel, or you can bind things to our gospel, or Gospel to cause the fungus to die. So those those are the main options. But actually having three different classes of drugs is not a lot when you've got all those different infections to take on board and you've got drug resistance to worry about. So we're not exactly over endowed with therapeutic options.

Lera 31:53
So when this Candida evolves, basically immunity from these antifungals is this cell wall changing and becoming more impenetrable, or like what's the mechanism behind their resistance.

Neil 32:11
So for those different classes of drugs, there are different mechanisms as a whole range of resistance mechanisms. For a zoals, there are two big ones. One is the target of the a zone, which is an enzyme, which is concerned with making components of the membrane that becomes changed mutated, so it doesn't bind it anymore. That's one. But it's also there's also mechanisms which they can induce these pumps in the membrane, which eject the drug out of the cell out of the fungal cell. So the fungus then becomes less susceptible. And there's several different drug pumps, which can be induced into some case by the presence of the drug. And the kick it out again, it's actually a same mechanism, that often leads to the failure of cancer therapy, where patients become increasingly less able to be controlled by the anti cancer drug, again, due to the induction of these pumps, which are busily getting rid of the drug that you're trying to use to treat the patient or getting rid of the antifungal which you're trying to use to kill the fungus. So the several things and also fungi can sometimes change the chromosomes they can add an extra part of a chromosome or an extra chromosome altogether, including drug resistant gene. So you can increase the copy number in the in the organism of a gene, which is protecting it against the drug. So his family are very, very difficult customers to deal with. They have many ways of avoiding the drugs, once which attack the walls again, we can change the target, you can get a mutation, which makes it non susceptible. Something we've worked on in our own lab as well as at some fungi. Also, when you attack it with a drug which attacks its wall. What it does is it builds another component of the wall which is not affected by the drug. So it compensates for the loss of one drug, one part of the skeleton of the wall, which would otherwise make it weaker by strengthening it by making it more robust by building another component of the wall. So they are slippery customers funghi and they have a whole range of resistance mechanisms.

Alex 34:23
I have kind of an interesting question for you. And as someone who studies, you know, fungal pathogens specifically on humans, I'm sure you have your own moral debates on you know how you feel about fungi, right? I'm sure you love the fungal Kingdom as you're talking about and you're passionate about it, but and I'm sure you get conflicted because a lot of the fungi you study kill a lot of humans, right. And so, you know, I love quarter steps. And I've been studying for many years and I feel a little disconnected because a lot of times they infect pests, right insects that cause a lot of destruction or death. And so it's almost like I'm rooting for the good guy sometimes. Right? And so, do you find yourself in this moral dilemma of, you know, wanting to love fungi, but at the same time, they almost play a bad, bad guy role or, you know, how, how do you? How do you feel about that?

Neil 35:24
Yeah, I'm a bit like you, I see both the good and the bad and funghi and both sides are fascinating and important. So I often point out that, you know, most people will use a fungal product every single day of their lives. And that's mainly things which they depend on. So funghi generate incredibly important drugs, penicillin. kappeler sporrans, Aunty, these are antibacterial antibiotics. We use drugs into induce labor to treat migraine to prevent drat graft rejection, calf cyclosporin we've got drugs that lower cholesterol levels like some of the statens we've got anti cancer drugs which come from funghi they attack souls. If you've ever had a candy or Sweetie, you've probably be eating something which is made so with citric acid which is produced by fungus. If you've clicked you put your clothes in a washing machine, you've been using fungal enzymes to get rid of the stains. You've eaten mushrooms, truffles, blue cheeses, miso soup, soy sauce, fungal proteins, like corn, which is a big industry. If you've ever had a beer or wine, a glass of Sacchi or a glass of whiskey, which of course as the Scotsman I love, they are all fungal products. And we use them to not only to do that we use them to germinate grains to make barley able to be used to ferment ferment things we use them to, to control plant disease, as well as that tried to stop them from decimating plants. Because they are You're right, the biggest agents of food security and plant disease on the planet.

Lera 37:14
Yeah, I always just remind myself it's an A whole kingdom and just like every other kingdom, we have great probiotic bacteria and then we have not so great and every kingdom is going to have this dichotomy of causing suffering versus not so overall, I think this just speaks to the power of a fungal organism and how adaptable and versatile they are. So I have one more like pathogen related question. And this is about schizo filan commune because with my research there seems to be one case of a fungus fruited. So most fungi that are infecting people don't create mushrooms. Because a filament commune does, and it has been found fruiting on soft palates of children and loans. Are there is this true that is the only fungus found fruiting on a human being and do you know of any other ones?

Neil 38:09
Well, shows up on community is a gorgeous organism actually a little bracket fungus which you can find on wood. And you're right it has been found on humans it can grow reasonably at 37 degrees. Often, routing is very rare as to form a mushroom or a spore or carp in some big macro substructure, you can see the eye that's very, very uncommon. There have been ones which have been found l like coprinus, which has an income node called copra Noxus. They've been described for example, in heart valves but actually the only see the fruiting once the heart valves been removed. It doesn't generally fruiting at 37 degrees, this is quite unusual. And and you know the, the fruit you see in the environment is generally in the autumn isn't in the sort of after the heat of the of the summer. But there are some other relatively rare cases, including SSA, copra Noxus. A few other cases of these higher funghi or the city, my seats, the ones that cause mushroom, farm mushrooms and toadstools, I just want to point out actually that cryptococcus is actually in the same group, and can form you know, spores and in the environmental phase. So although it's not a yeast in the body, it has the full lifecycle including the sexual lifecycle which produces these fruiting bodies outside the human body. But, mercifully, almost none of the mushrooms and toadstools cause infectious disease on them, of course, because toxic disease but not infectious disease.

Lera 39:59
So I want to flip the table and see if you have any. I mean, we kind of alluded to this already, fungi can be good for us. And you can find a lot of really great compounds to fight against other fungi that are causing problems. But is there any cases in particular that you want to highlight? Like maybe there's a species of fungi found in everyone's ears that are preventing your infections, or, you know, any kind of microbiome question or microbiome highlight that you want to talk about?

Neil 40:32
Well, there are a lot, there's a lot of interest in the micro biome, which are all the bugs, mainly bacteria that live in the human gut, predominantly. But there's a micro biome that you can study on the skin or in the lungs, or in the hair, anywhere you choose to look. What we know, from recent researches, there's a lot more funghi in the that are associated with the human body, causing no disease just normally carried by the human body, then we suspected and there's some very nice work going on on the myco core biome in the gut. And there are several groups of organisms in there. Some of them may be relatively neutral, some of them might not be good for us, certainly at certain stages, or they might be a reservoir for potential infection. If, for example, the immune system collapses for some reason. But to my knowledge, there's not so many examples, the fungus as a very positive effect on humans. But I would say never say never, we don't really know. We know that having a healthy microbiome, including funghi, is protective in general from pathogens entering the gut and causing problems. And it may well be that the funghi in the gut have a positive contribution to make there and defending ourselves against organisms which could otherwise do us harm. We also do know that funghi can sometimes cross the the barrier, the mucosa in the gut, and cause unsuspected diseases. So in for example, a rather curious one, which is published relatively recently was it was shown that for some people who had alcoholic liver syndrome, that this was being made worse by the fact that members of the funghi from the gut were being able to cross across the damaged epithelium of the gut, get into the liver and cause inflammatory disease. And part of the evidence that this was due to the fungus was quite an obvious experiment, that those people who have alcoholic liver disease respond very well to antifungal drug treatment. So that, you know there, the microbiome in us is an incredibly important vibrant field of research for the moment. And there's some terrific work being done around the world in this area. But they're scratching the surface of what we know at the moment, there's an awful lot more to be done.

Alex 43:18
I heard a story and I don't know too much about it. But apparently, criminal investigators are looking at the micro and micro biome to solve cases, and basically can detect whether a person was in a room based on the bacteria and fungi that they read behind. Have you or any colleagues, have you heard of this before? And have you done any work? solving any criminal cases?

Neil 43:46
No, but I have had a chance to meet a couple of people who are forensic microbiologists. And, for example, they have been able to show that this person couldn't have died here because the fungus which is in their lung could only have come from a water environment. So they must have been a cow or a river. Or, you know, that that the organisms on their on their surface were completely compatible with organisms you'd find in their their home, for example. So each fungus has got a genetic signature, which can be helpful just like the genetic DNA fingerprinting of of humans can be, be helpful. So I have no doubt that they will play their part in criminology as well.

Lera 44:35
That's the future of forensic forensics, for sure. So I'm curious about where you look for antifungal drugs. I mean, do you look for them in other fungi when I picture two fungi on a petri plate? You know, there's like a enzymatic warfare going on at the point of confrontation and yes, like how do you pioneering this discovery?

Neil 45:03
Well, for those who do this, they're there, they will use everything that makes sense. So any approach. So clearly funghi are themselves the source of antibiotics. And the original one penicillin come from Penicillium is the obvious example of that. But there are there are others. He kind of candance I mentioned, they are fungal products, which act against other funghi. So you're right, that fact, because organisms are in warfare for each other, they have defense systems to protect them. So you can turn that around and use that to our advantage. So there's a lot of work studying natural products. And the thing about the diversity of funghi, I mentioned that, you know, 5 million species or more, actually, we've only ever cultured a tiny number. And we only described, you know, a very small fraction of that whole biodiversity. So amongst that biodiversity, they're almost certain to be new metabolites and things and include amongst those will be anti microbial drugs that we have not yet found. That's not easy work, though, you tend to rediscover the same drugs time and time again. So increasingly, you're looking for a needle in an ever expanding haystack when you do that. The other type of work that's done, which has also been very productive, and there's a lot of very useful advances being made at the moment is to either modify a drug which we know as good activity and try and make new activities, BB changes spectrum of activity, as done been done, done a lot, both with natural products, and with drugs, which are made in the laboratory, the easels don't come, for example, from other organisms, they are made by chemists, and chemists modify the structure of vessels, they're modifying the structure of kind of candidates motor, new mechanic and and coming out through the system now, which is got improved properties. And you don't need to inject it as many times it's a drug, which kind of candidates generally are IV drugs, you inject them. And if you're being treated with them, you don't need to be in the hospital, because you need to top up every day. So there's a new, modified drug, which you'll need to top of every week, which obviously will make it easier for patient care. So there's a lot going on in that sector. I mentioned that we have not got any vaccines to back that up. And another big area, which we really need to do more with which there are some exciting opportunities for is tweaking the immune system to work with us more effectively to eliminate the fungus, sometimes cause disease because our immune systems aren't quite up to the job. But you can give the immune system a help. You can augment or support the immune system with secondary treatments, which can make that combination of the natural immune system and the alterations you you add with drugs more effective, and there's some really nice opportunities in that area coming from fundamental studies. Understand understanding why it is immune system sometimes is blind to the presence of a fungus.

Lera 48:27
That makes sense. I've kind of a question from left field that's not necessarily related to this. But since your your formal training I'm just curious. I know a lot of fungi secrete catenis and other enzymes to you know, infiltrate some substrate, but in particular within the case of catenis What's the mechanism behind a fungus? releasing Guyanese, but it not like consuming itself? Because it's cell wall is also made of cotton. How does that work?

Neil 48:58
Yeah, that's such that's a great question. I spend a lot of my time in the past and even though working on on cotton. So very important structure. It's a it's a toughest thing that nature's ever made in a weight for weight kaiten, which is what you put in the wall of a fungus. But it's also what makes a crunchy cockroach or an insect or an arthropod or a mollusk. It's all those those bits of things, you get Katyn in the squid pen. And these are it's a polysaccharide. But it's wait for weight stronger than stainless steel. And it's incredibly tough partly is tough, because first of all, it's a linear polysaccharide which is very unusual on the cellulose and on an kaiten form linear chains of sugars. And then it folds back in itself back and forward, back and forward and bonds together. So it's a bit late when somebody makes a samurai sword when it's for the metal. folded back ends and molded together, it makes an extremely strong structure. And those are what the fibrils are in the wall. And they're extremely tough. So funghi protect their own Katyn very well, often they have a layer outside the wall, the kaiten layer, which is impermeable to enzymes getting in, and that's one of the major tricks. So even if a fungus is secreting catenis, it sticks it on the outside as quickly as possible, and then prevents it getting back in. So it's not hanging about in its own wall digesting it, otherwise it would cause problems. And as you know, a lot of funghi are now being used quite successfully, to attack insect pathogens as a type of so called biological control. And part of their successes, they're able to attack the skeleton of the insect which is essential for life, which is made of Katyn with their Katyn aces. And they often have additional toxins as well, which get rid of insects and in fact, insects are pretty in pregnant to most things. And the probably the only group of organisms they seriously fear are the funghi.

Lera 51:15
fungal enzymes, man, there's some powerful stuff. Yeah, thank you for that little kaiten explanation that was that was really cool. I did not know that fact that wait for Wait, it was stronger than stainless steel. But I'm not surprised. I feel like every other day, I get my mind blown in some capacity with fungi. Are there any other things that you want to share?

Neil 51:38
Well, I think one thing that I would just say is that we are in a situation in medical mycology my area where we just don't have enough raw recruits in the lab. And and partly that is just an accident of history, that what changed the world fundamentally, in many ways, was HIV. So each IV led to a lot of people who were otherwise would have been completely healthy being very immunosuppressed and of course by this by this virus, but they also started to become susceptible to fungal infection. So it HIV led to a very large number enhanced number of people getting oropharyngeal. So that's throat thrush infections. And in fact, it used to be sort of almost diagnostic, if you adopt too, if you before we got HIV effective track treatment underway. What people would see and alert them to the probably the problem might be that they had this. So now that only goes back to the 1980s. So in terms of training, new generations of microbiologist that I can the impetus to do that really took a big boost then but it's only gone through a couple of you know, generations academic generations since then. So it's an incredibly interesting and important component under appreciated. And even to this day, you often get very frustrated as medical mycologist that, that the function get forgotten about, even though so explained to you. That's completely inappropriate, because the burden is so high. So if anybody is really interested in what to do with their immunology, what to do with their microbiology, or their skills in biochemistry, imagine all the students that might be listening to you who are going to universities studying these fundamental processes. You know, they could do a lot worse by coming and getting in touch with people who are studying fungal infections where they could really make a potential a big difference.

Lera 53:44
Thank you for sharing that. And you know, we're at telluride. Right now Alex is about to give a few presentations. And we'll definitely be spreading the word that there is a lack in the medical mycology field. So there are a lot of young people out here who are interested and have degrees in biochem. And you know, things that are very reasonably eligible to pursue

Alex 54:05
this field. We actually just met someone who has their degree in biochem, and got an opportunity to study Candida in France, and she was unsure if you wanted to take the opportunity and I think right after this episode, or tell her to definitely take it and contact you to help this field that is so needed.

Neil 54:31
I think it could have a very exciting and worthwhile career that could really make a difference.

Lera 54:39
It's few and far between for how serious these issues can be. So thanks for your work on behalf of the world. And I got just all the delightful knowledge that you shared with us.

Neil 54:50
While it was wonderful to speak to you, I always like to speak to colleagues who are fascinated by the fungal kingdom. I say it's got a lot to offer and it Not just the bad guys, you know, there are fabulous things to see and to, to learn about which have not been even touched on. And I think a lot of people think of medical mycology is just being things like athletes food, but it's not been like that for many years. And that doesn't sound that exciting although it does actually cause billions of dollars of problems a year. And there's an awful lot more that can be done.

Lera 55:28
Lovely. Thank you so much, Neil. Once again,

Alex 55:31
Big thanks to Neil Gao. Big Thing See you all remember you can help us by rating and reviewing or just even telling your friends or bagger at your grocery store. We will shout you out on our show one review a week if you want to get featured. And as always, much love and Minda spores be with you.