The Mould Show

5 Fungal threats you might have missed due to COVID-19

June 06, 2020 Dr Cameron Jones Episode 50
The Mould Show
5 Fungal threats you might have missed due to COVID-19
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The Mould Show
5 Fungal threats you might have missed due to COVID-19
Jun 06, 2020 Episode 50
Dr Cameron Jones

With all the attention at the moment focussing on the SARS-CoV-2 virus, the rest of microbiology has taken somewhat of a backseat.  While the COVID pandemic has restricted behaviour and led to 6.4M cases and 383,000 deaths, the number of illnesses and deaths caused by fungi is also of epic proportions at 800M and 1.6M deaths annually.  With global warming a serious problem for humanity, I want this week to discuss some of the reasons that fungi are often neglected.  I want to shed some light on why this is, and what we should be discussing.  We'll look at forced evolution in the lab and why Temperature optima may well turn out to be the best predictor of the next fungal plague or infection illness.  Will it turn on us or our agriculture crops?  Thats the crux of food security - and mycotoxins and other direct infections do more than reduce our access to bananas!  I'll also make a short review of some of the fungal catastrophes to put this into context as well as discuss what we know about COVID and co-infections from Aspergillus fumigatus.

Topics:

1. Fungi are under-appreciated as a source of infection and co-infection. Viruses are now easily understood to be a source of infection between people and most people understand the concept of hospital acquired bacterial infections, but…

2. Fungi have significant genetic flexibility and rapid evolution

3. Global warming and fungal disease, invasive fungal infections after natural disasters

4. Plant and agricultural fungal threats much better understood - food security impacts potentially devastating

5. Short history of catastrophic events caused by fungi  

REFERENCES:

Casadevall A. Global Catastrophic Threats from the Fungal Kingdom. Curr Top Microbiol Immunol. 2019:21-32. doi:10.1007/82_2019_161

Case N, Heitman J, Cowen L. The Rise of Fungi: A Report on the CIFAR Program Fungal Kingdom: Threats & Opportunities Inaugural Meeting. G3:Genes|Genomes|Genetics. 2020;10(6):1837-1842. doi:10.1534/g3.120.401271

ALL ABOUT GAFFI: Fungal diseases are neglected worldwide by public health authorities. Gaffi.org. https://www.gaffi.org/. Published 2020. Accessed June 6, 2020.

Lovett R. Space station mold survives 200 times the radiation dose that would kill a human. Science | AAAS. https://www.sciencemag.org/news/2019/06/space-station-mold-survives-200-times-radiation-dose-would-kill-human#:~:text=Astronauts%20on%20the%20International%20Space,where%20radiation%20doses%20are%20low.&text=The%20gray%20is%20a%20measure%20of%20the%20amount%20of%20absorbed%20radiation%20energy. Published 2020. Accessed June 6, 2020.

Pomeroy R. Fungi That 'Eat' Radiation Are Growing on the Walls of Chernobyl's Ruined Nuclear Reactor | RealClearScience. Realclearscience.com. https://www.realclearscience.com/blog/2020/02/04/fungi_that_eat_radiation_are_growing_on_the_walls_of_chernobyls_ruined_nuclear_reactor.html. Published 2020. Accessed June 6, 2020.

Carbone C. Surprising find in Chernobyl reactor. NewsComAu. https://www.news.com.au/technology/science/evolution/melaninfilled-fungus-thriving-on-radiation-from-chernobyl-meltdown/news-story/15af9f34faa4b62dff46a1258dbfb235. Published 2020. Accessed June 6, 2020.

de Crecy E, Jaronski S, Lyons B, Lyons T, Keyhani N. Directed evolution of a filamentous fungus for thermotolerance. BMC Biotechnol. 2009;9(1):74. doi:10.1186/1472-6750-9-74

Leach MD, Cowen LE. Surviving the heat of the moment: a fungal pathogens perspective. PLoS Pathog. 2013;9(3):e1003163. doi:10.1371/journal.ppat.1003163

Dale, J., James, A., Paul, J. et al. Transgenic Cavendish bananas with resistance to Fusarium wilt tropical race 4. Nat Commun 8, 1496 (2017). https://doi.org/10.1038/s41467-017-01670-6

Show Notes Transcript

With all the attention at the moment focussing on the SARS-CoV-2 virus, the rest of microbiology has taken somewhat of a backseat.  While the COVID pandemic has restricted behaviour and led to 6.4M cases and 383,000 deaths, the number of illnesses and deaths caused by fungi is also of epic proportions at 800M and 1.6M deaths annually.  With global warming a serious problem for humanity, I want this week to discuss some of the reasons that fungi are often neglected.  I want to shed some light on why this is, and what we should be discussing.  We'll look at forced evolution in the lab and why Temperature optima may well turn out to be the best predictor of the next fungal plague or infection illness.  Will it turn on us or our agriculture crops?  Thats the crux of food security - and mycotoxins and other direct infections do more than reduce our access to bananas!  I'll also make a short review of some of the fungal catastrophes to put this into context as well as discuss what we know about COVID and co-infections from Aspergillus fumigatus.

Topics:

1. Fungi are under-appreciated as a source of infection and co-infection. Viruses are now easily understood to be a source of infection between people and most people understand the concept of hospital acquired bacterial infections, but…

2. Fungi have significant genetic flexibility and rapid evolution

3. Global warming and fungal disease, invasive fungal infections after natural disasters

4. Plant and agricultural fungal threats much better understood - food security impacts potentially devastating

5. Short history of catastrophic events caused by fungi  

REFERENCES:

Casadevall A. Global Catastrophic Threats from the Fungal Kingdom. Curr Top Microbiol Immunol. 2019:21-32. doi:10.1007/82_2019_161

Case N, Heitman J, Cowen L. The Rise of Fungi: A Report on the CIFAR Program Fungal Kingdom: Threats & Opportunities Inaugural Meeting. G3:Genes|Genomes|Genetics. 2020;10(6):1837-1842. doi:10.1534/g3.120.401271

ALL ABOUT GAFFI: Fungal diseases are neglected worldwide by public health authorities. Gaffi.org. https://www.gaffi.org/. Published 2020. Accessed June 6, 2020.

Lovett R. Space station mold survives 200 times the radiation dose that would kill a human. Science | AAAS. https://www.sciencemag.org/news/2019/06/space-station-mold-survives-200-times-radiation-dose-would-kill-human#:~:text=Astronauts%20on%20the%20International%20Space,where%20radiation%20doses%20are%20low.&text=The%20gray%20is%20a%20measure%20of%20the%20amount%20of%20absorbed%20radiation%20energy. Published 2020. Accessed June 6, 2020.

Pomeroy R. Fungi That 'Eat' Radiation Are Growing on the Walls of Chernobyl's Ruined Nuclear Reactor | RealClearScience. Realclearscience.com. https://www.realclearscience.com/blog/2020/02/04/fungi_that_eat_radiation_are_growing_on_the_walls_of_chernobyls_ruined_nuclear_reactor.html. Published 2020. Accessed June 6, 2020.

Carbone C. Surprising find in Chernobyl reactor. NewsComAu. https://www.news.com.au/technology/science/evolution/melaninfilled-fungus-thriving-on-radiation-from-chernobyl-meltdown/news-story/15af9f34faa4b62dff46a1258dbfb235. Published 2020. Accessed June 6, 2020.

de Crecy E, Jaronski S, Lyons B, Lyons T, Keyhani N. Directed evolution of a filamentous fungus for thermotolerance. BMC Biotechnol. 2009;9(1):74. doi:10.1186/1472-6750-9-74

Leach MD, Cowen LE. Surviving the heat of the moment: a fungal pathogens perspective. PLoS Pathog. 2013;9(3):e1003163. doi:10.1371/journal.ppat.1003163

Dale, J., James, A., Paul, J. et al. Transgenic Cavendish bananas with resistance to Fusarium wilt tropical race 4. Nat Commun 8, 1496 (2017). https://doi.org/10.1038/s41467-017-01670-6

Hello, and welcome to this week's edition of The Mould Show. My name's Dr. Cameron Jones and I'm an environmental microbiologist. And certainly for the last couple of months, all of us have been preoccupied with the COVID-19 pandemic. But because I'm an environmental microbiologist, today I'm going to be getting back to talking about fungi. And in fact, I'm going to be talking about five aspects of fungi and why they are such a significant threat to us from an infection and allergy point of view, but also in terms of their impact on crops and food security. And I'm going to be going through some of the reasons why fungi are considerably neglected. And certainly, as we've seen with the COVID-19 pandemic, people are talking about the fact that humanity and policymakers were very much underprepared for this significant threat. I would argue that scientists are significantly underprepared for the impact that fungi have on society and on public health and so that is going to be the focus of the live stream today.

So, what we're going to be covering is the fact that they are an underappreciated source of infection and certainly coinfection. What do I mean by this? Well, I want to put some statistics on the table and I want to review some of the emerging literature to back up my argument here. And so, all I have to do is go into Scientific American, for example, and I can find that, yes, a lot of COVID-19 cases, a lot of these patients, their lung infections, there is another type of infection, not just the SARS-CoV-2 virus affecting them, but they're also being, in a sense, impacted on by fungi such as Aspergillus fumigatus, which is the infamous fungus which causes aspergillosis.

And certainly, a couple of months ago, I put out a paper in the peer reviewed literature focusing on the environmental role of fungi as a complication in the COVID-19 cases. I set forth a range of different issues which clinicians should be aware of and this is being supported by more recent publications focusing on this as well. More recently, even a couple of weeks ago on Twitter, in social media, a scientist in a pathology lab was able to get a pure culture of Aspergillus fumigatus from a COVID-19 case two weeks after they had been admitted to the intensive care unit. And so, we know from COVID-19 cases that they overwhelmingly impact on lung function when those individuals are admitted to intensive care. And in a sense, there are these other microorganisms like fungi, which could potentially be impacting on people's recovery as well. And so, there are a range of different publications that are emerging week by week to support the fact that even with our COVID-19 crisis, hospitals and clinicians should be very aware of the potential of other microorganisms to be impacting on the health and wellbeing of these particular patients.

And so, I can find other examples of this. And again, four or five months ago, it was only the issue of the virus, but now the other microorganisms are coming into focus. This is a very good thing because it may mean that there are improved treatments and potentially even improved screening before people become susceptible to exposure to this particular virus. Again, I can pull out a key result from a paper, which just came out on the 27th of April 2020 in the journal Mycoses, and they were saying that five out of 19 consecutive, critically ill patients with airway obstructive disease had pulmonary aspergillosis caused by Aspergillus fumigatus.

Now, the context for today's show is that certainly because of the COVID-19 crisis, viruses are much more easy to understand. Everyone, in a sense, has had a crash course in various different aspects of the theory and experience of what it is like to have a epidemic occur and for infection to be on the mind of everyone. But most people also prior to COVID-19 understood that many people become sick due to hospital acquired infections and this concept of multidrug resistance due to the fact that, in a sense, the microbes have evolved to evade the ability to be acted on by these antibiotics and also various different cleaning agents, which lead to antibiotic resistance.

And so, in a sense, with COVID we understand about the transmission more acutely and prior to COVID, we understand that hospital acquired infections occur. But fungi, in a sense, are completely underappreciated. And certainly in my work on a day-to-day basis, I'm constantly reminded about the impact that these microorganisms have on people. For example, the person that sent in this mould test kit, they were concerned about whether or not to keep their seagrass dining chairs. And so, this individual was concerned about whether or not she should keep them. You can see that the results are quite insightful in terms of the level of contamination.

In any case, I digress a little bit, but the point that I want to make is that these microorganisms are all around. My microscope behind me actually has up on screen a tape lift, something that we do all the time to work out whether or not a particular surface is contaminated with microorganisms. Because we have to appreciate that microbes are all around us, just as viruses are all around us. They don't always cause adverse health symptoms, but in certain circumstances we can. And that's what I want to talk to you about today.

And so, before I get into this about the fact that humans are relatively resistant to infection by fungi, I just want to talk about the environments that these fungi grow best in. We know, for example, that fungi like a source of food. In this case, the top panel on the left hand side shows some framing timbers in a new home construction. So, if you can imagine you undertake to build a home. In this particular case, the owners and the builder elected to have a timber frame construction, and eventually the internal plasterboard walls will frame up that house and make beautiful rooms. But during construction, the frame got excessively wet and mould grew on the timber framing.

If we take something called a tape lift and then put it under the microscope, we can, in a sense, open up Pandora's box and see exactly what is growing on those framing timbers. In that example, the builder insisted that this was just normal mould and that it just occurred due to the fact that unfortunately the frame got a little bit too wet, but it wasn't really going to cause any significant impact on the family long-term. I would argue that that's not true and there is some significant potential for hidden mould within frames of buildings to cause quite potentially serious problems down the track, especially if there are further plumbing problems or defects down the track which allow water to get into the wall cavities and come into contact with those framing timbers.

But why are humans particularly not susceptible to a direct infection? Usually you need to be immunocompromised in some way. The reason for that is that these fungi that tend to grow out in the environment grow at what's called ambient temperature and that is the lower temperature than what temperature we have. And so, if we consider those microorganisms that have a temperature optima lower than our temperature, well, they're the ones that we find out in the environment all the time. And so, in a sense, unlike bacteria fungi tend to grow at a lower temperature, but this is changing and we're going to discuss today some of the reasons why this is changing.

So in the main, when you have fungus growing on building structures, for example, or on these seagrass chairs, or potentially on any water damaged building element in my office, or my home, or anywhere else, in a sense they're growing at a lower temperature. That means that you can still have an allergy to the spore or an allergy to the cell wall fragment if it becomes aerosolized. But the number of direct infections caused by fungi is relatively low and that is a wonderful thing. But it should be recognized that fungi cause approximately 1.6 million deaths per year. When we take into consideration all the other illnesses and diseases caused by environmental and opportunistic fungal pathogens, there are 800 million people affected by fungi on a yearly basis. To put that into context with the COVID crisis, we've had 383,000 deaths from COVID and 6.4 million cases of COVID worldwide.

Now, fungi have excellent genetic flexibility and they can rapidly evolve. So, there are approximately five million fungal species known, give or take, and they are found growing wherever there is a suitable food source like my Petri plates or the framing timbers in that house example I gave you, and at the correct temperature. They have been found in a lot of diverse environments. This issue of temperature is called thermo-tolerance. They also can survive quite significant levels of ionizing radiation and other types of radiation. So, they've been found on the International Space Station growing on the walls there, four or five kilometers from Earth, and they've also been found deep underground and also growing on radioactive waste.

Now, essentially fungi are decomposers. Like with the timber frame example, they love growing on wood. They grow on the sugars in wood, the lignin and the cellulose, and then extract that as energy that allows them to grow. Now, that's why they love water damaged buildings. We all know that fungi can be adapted by humans to create value added products. These are called secondary metabolites and the most well-known secondary metabolite from fungi is penicillin. But other types of secondary metabolites are like some of the mycotoxins that are growing on these Petri plates. These mycotoxins are variously carcinogenic or neurotoxin producers and they can create significant impacts on human health. But the key thing about fungi is that they do not need a host to survive. With the viruses, they must replicate in a host. And so with fungi, this makes them very different to a lot of other microbes as well.

So, the key takeaway from this introduction to the talk today is that human pathogenic fungi are not likely to cause catastrophic problems for humankind unless there is a severe decline in the immunity of a population such as clusters of HIV, or the slow epidemic of heart disease due to obesity, diabetes, and a lack of exercise, and poor diet. And cancer, of course, leads to long-term immune dysfunction and makes people susceptible to another range of infections. But it should also be recognized that fungi can potentially be weaponized as well. And certainly, I would argue that the pandemic, at this point in time, leads to a situation where we need to be very mindful of the co-occurrence of coinfections of fungi and other bacteria. Because, in a sense, there is a lot of people now who are susceptible to other types of infections, so we need to be aware of that.

Now, this issue of global warming and fungal disease, I want to touch on this as well, as well as natural disasters like floods and those sorts of waterborne, natural disasters. Global warming essentially impacts on the fungal population because as temperature increases it means a lot of these microorganisms that grow at ambient temperature are being forced to grow at slightly higher temperatures. This is really, really, really interesting because we know from the fungal taxonomy out in the environment that your white rot fungi and your basidiomycete fungi very well able to grow at higher temperatures. And certainly, the microorganisms that grow, for example, in compost heaps grow at very high temperatures.

And so, what is causing these fungi to adapt? Because if they start with adapt and are able to tolerate these higher temperatures, they can quite easily become more serious pathogens for people. This has big implications for public health as well as for food security. And so, I draw your attention to a publication which came out back in 2009. This is a very, very interesting study because the scientists were trying to force fungi to adapt, that is force them to become more thermo-tolerant or to put it in lay language, make them grow at higher temperatures. As you can appreciate, if they can grow at the same body temperature as us, that's a real problem because that means that they could use us as a food source and, essentially, that can cause illnesses from these production of secondary metabolites, these mycotoxins and all of that going on.

And so, in this publication, what the scientists did is that they developed a particular type of continuous culture system which forced the fungus to adapt. What they did is they found that in four months, or 22 life cycles of the fungus, they were able to get two fungi that were thermo-tolerant and were able to now grow at the higher temperature. That is really significant because they were able to not only grow, but they were able to reproduce at that temperature. And importantly, they were able to retain the pathogenicity at this higher temperature. This is a wonderful example of how directed evolution could theoretically impact on human health by more fungi being able to adapt to higher temperatures. And so, the conclusion of the research was that the filamentous fungi were able to adapt.

When you think about this concept of adaptation, I need to draw your attention to something that everyone can understand. Because, just say you don't get the concept of fungi adapting. Well, moths in England, when they were exposed to higher and higher levels of pollution, the trees ended up, or some of the trees ended up, becoming covered in the pollutant, meaning that these moths that were originally white were more easily able to be a food stuff themselves. And so, the moths adapted to their environmental conditions and there was a particular mutation that went through the moth population which was advantageous for the moths. And some of them turned from white to black, meaning that they were now able to be camouflaged against the pollution contaminated trees. So, this concept of adaptation is very important to understand that it's something which is beneficial to the microorganisms or the group of microorganisms as a whole.

And so, if you can deliberately increase the temperature or thermo-tolerance of the fungus in the lab, imagine what global warming is doing to all the different fungi which are out there, that is those five million species. Remember, it took only four months in the lab, 22 life cycles, to select for a new temperature optima. So, this could potentially be happening now. And these fungi could potentially be as impactful on human health and food security as the COVID-19 impact has been on us. And so, I want to quickly draw your attention to a couple of buzzwords, which I think you're going to see increasingly in the public health and microbiology literature. Certainly, we have Aspergillus fumigatus, the cause of aspergillosis. We have cryptococcus neoformans. Again, these are these hybrid yeasts, which are implicated in a lot of new infections in immunocompromised people. And there is a lot of academic research going on about this, which should be understood and considered as well.

Now I want to talk about plant and agricultural fungal threats, because these are much easier to understand in many cases than adverse health conditions. So, all of you would be familiar with bananas. Well, a couple of years ago, a common fungus called Fusarium ripped through the banana producing countries worldwide, leading to significant economic impacts on the commodity trade of these bananas. As you can appreciate, everyone likes bananas. I've shown a picture of the queen being handed a particular type of banana, this Cavendish banana, which is so highly prized worldwide. And as you can appreciate, as the fungus went through this population worldwide, what do you think is going to happen to the prices? Well, the prices are going to go up.

Imagine if these fungal threats affect other crops, as they do, as they affect rice and all sorts of other crops. The impact from fungal mycotoxins on crop losses is considered to be up to, I think it's about 30% of crops have to be thrown away due to the fact that they get contaminated either during growth or soon after harvest. And so, the impact of fungi on food is absolutely really big and fundamental. We can't forget this because if we interfere with the food supply, that is going to have huge tipping points to health in the main, and that will affect us globally. I have put up some good news here because a beautiful Nature article came out showing how the scientists were able to select for a particular variety of this Cavendish banana, which was resistant to the fungal predation.

Now I want to go through a short history of catastrophic events caused by fungi. And again, I'm drawing from a publication which I have cited in the reference lists, that it's going to be at the bottom of this live stream and the podcast as well. Fungi have had a huge impact on human health for millennia. We can go back to something called the tenth plague that was visited on Egypt. Strains of Aspergillus and fumigatus were known through history to have caused these significant mass casualty events back then, really many, many, many centuries ago. Fusarium, as you saw with the impact on the bananas, was also known to have been the causative agent of the plague of Athens. And there have been a range of different impacts of mushrooms that have been considered toxic but by accident ingested and caused significant problems for people.

Also, everyone's probably heard of the famous potato blight, which affected the potatoes. This was originally considered to be a fungal microorganism. It has been more recently, with molecular taxonomy, been reclassified, not as a fungus, but as an oomycete and this is more similar to an algae. But nevertheless, it is a filamentous microorganism which was responsible for the destruction of the potatoes and caused a massive famine as well. Another Fusarium species in the 1930s caused over 10,000 people to be affected with 60% of them dying in the 1930s. Whereas, we also mustn't forget a couple of years ago, a whole lot of pharmaceuticals destined to be used for spinal taps became contaminated during the logistics of the fact that these preparations, the ampules, were in cardboard boxes. Those cardboard boxes were stored in refrigerators. Those refrigerators and the cardboard boxes became mould contaminated. Then when the ampules were broken, some of the mould that had penetrated the cardboard box and grown over the glass ended up inside, then being sucked up into the syringe and then injected directly into the patient, causing this significant steroid contamination event seven or eight years ago.

Then we get on to the floods and hurricanes and even the burst pipes in our homes. All of these are examples of events which are, in many cases, outside our control, which mean that fungi are brought directly into contact with us. And so, that's what I wanted to cover today in the main, the fact that fungal microorganisms are able to adapt, that they are growing closer and closer to human body temperature as global warming becomes more significant, that it is possible in the lab to select for certain strains of fungi that show greater thermo-tolerance, and that this could be a huge problem for public health. Increasingly in the literature, we are seeing publications come out showing that fungi like Aspergillus fumigatus are responsible for some of the significant lung impacts. Up here on the screen now, I've got a couple of the key papers which I've shown and talked about today. I want to draw your attention to a wonderful organization called Gaffi, G-A-F-F-I, .org. This organization is all about focusing attention on fungal diseases and the impact that fungal diseases have on human health and also on food security.

In closing, I'd like to say that hopefully in Australia, we're behind the worst of the SARS-COVID-2 pandemic. I think all of us need to be mindful of the impact of other microbial threats. I also am of the firm opinion that from a research position, as well as an educational foundation, that microbiological literacy needs to improve across the board along with our understanding of the role and the fundamental research about fungi. We need more research dollars into microbiology and especially into mycology because I didn't even mention the fact that the bat population has been significantly impacted on by fungi.

In some locations of the world over 75% of bats have disappeared. Now, bats have got a bit of a bad name because of their supposed vector relationship with the COVID crisis. But the thing is that large populations of organisms and potentially humans are being impacted on by fungi all the time, it's not just water damage, and they are becoming more virulent. So, it's something to think about. In any case, I hope you have a great week and I'll be back next week with more for The Mould Show. Bye for now. See you later.