Discovering New Ways To Fight Fungal Diseases That Threaten Our Food Security & Health - Dr Neil Brown

The Director of the Milner Centre for Evolution, Professor Turi King, talks to Dr Neil Brown, whose research focuses on discovering new ways to fight major fungal diseases that threaten our food security and health.

Episode Transcript

(00:02):
Hello and welcome. You are listening to a podcast by the Milner Centre for Evolution at
the University of Bath. I'm Professor Turi King, your host, and today I'm talking to Neil Brown,
who is a fungal biologist whose research focuses on discovering
new ways to fight major fungal diseases that threaten our food security and health.

(00:25):
Neil, for people who don't know what is a fungus? I know there are supposed
to be about 5 million species of them.Well, that's actually a very difficult
question because fungi are very diverse. So, you could have a unicellular yeast, which you use to
make your beer and your bread, or you could have some mycorrhizal fungi network connecting all of

(00:46):
your trees, or you might have those mushrooms, which are multicellular fungi that have come
together to form these beautiful mushrooms that are their sexual reproduction structures.
So, what unites all of those fungi is their osmotrophs. So, that means that
they vomit on their food, degrade it all, and then suck it all back in. So,

(01:11):
they secrete lots of enzymes to digest their food on the outside, and then they absorb it.
So, in the past, people thought fungi were more related to plants because a
mushroom looks more similar to a plant than it does an animal. But in fact,
they're actually more related to animals, now we have better technologies to understand them.

(01:34):
So how did you become interested in fungal biology?
So, I originally wanted to be a marine biologist because I'd spent a year working in a conservation
company, scuba diving off a coral reef in the Caribbean, which sounds amazing,
and it was. And I was due to go to Queensland in Australia to work on the sonar of sharks’ noses,

(01:56):
and at the last minute the funding fell through, and I didn't have an opportunity to go to.
And then I saw this advert, go to Costa Rica, work for Cadbury's on the biological control of
a disease of the chocolate plant. And I was like, okay, that sounds fun. So I went to Costa Rica,

(02:17):
and I had to work on spraying these microbes on to cacao pods in plantations
and controlling these diseases of the crop.But I saw the impact that these diseases had
on the small farmers livelihoods, because they could lose 95% of their crop and suffer real

(02:38):
hardship. So that motivated me to switch from marine biology to food security.
So, how does a fungus attack a plant and why does it attack a plant?
So, fungi can attack plants in many ways. They could be infecting roots through the soil. So,

(02:58):
they might sense things secreted from a plant's root, managing to grow towards it, and then tap
into the plant and cause death and destruction in a diverse amount of ways. Or they could be blown
hundreds of kilometres and then fall down in the rain on a susceptible crop and cause disease of

(03:21):
some aerial plants, whether that be attacking the roots or it's attacking the leaves, it's looking
for ways into the plant, when it can then either live for some period of time in association with
the live plant and obtain nutrients from it while it's growing, and then sporulating and spreading

(03:44):
on to the next one. Or it can go in and cause absolute destruction straight away and absorb
all of its nutrients from the dead plant.Are they causing disease within
us if we then eat those crops?If we look at the fungi that infect plants,
it's not our eating of the infected food and the fungus then growing out from that that is causing

(04:10):
us a problem, it’s the fact that the fungus inside that food might have produced lots of
toxins called mycotoxins, and then these can have a whole load of negative impacts on your health.
They can be some of the most carcinogenic compounds that we know of, or they can affect your
immunity. They can cause lots of gastrointestinal kind of disorders. And in small children,

(04:37):
which are particularly vulnerable, it can cause stunting in their growth.
And it's not just humans that are affected; it's animals as well, isn't it?
Yeah. So, in developed parts of the world, we have quite good food safety systems in place. So, we
monitor, say, a cereal crop arriving at a miller for the presence of these mycotoxins. And we set

(05:02):
quite strict limits for the presence of these known toxins in our food. But there are parts of
the world where people are less protected because it's less of an industrial agricultural system,
more of a subsistence farming type of model. And there you can have acute exposures of people to
mycotoxins, where it can cause fatalities.So, we can already see the applications of

(05:29):
your research in terms of looking at fungi. And I know you're concentrating
on two different pathogens. So, what are they and why are you concentrating on those?
So, in our lab we work on Aspergillus species and Fusarium species.
Fusarium can infect the crop when it's in the field and produce lots of these toxins. And it's

(05:55):
mainly a serial infecting problem. We are most interested in cereals because we gain most of
our calories from cereals in our society.And Aspergillus is more of a post-harvest
problem where it can make your food mouldy when not being stored correctly,
and then also infect it with mycotoxins.So, they're mainly a pre- and post-harvest

(06:21):
problem in our cereals, and probably 70% of our cereals have toxins from these fungi in them,
5 to 20% probably have levels that are beyond what is recommended for human consumption. And
then that gets downgraded for animal feed. So that costs the cereal farmer money. But

(06:44):
we don't have as rigorous guidelines for some of these toxins for animal feed. So, we pass on the
problem to our farmed animals. But then they also have the similar health consequences on them. So,
a livestock or poultry farmer might have a problem with his animals not growing as quickly
or experiencing reproductive disorders.So how does Fusarium spread then?

(07:10):
So, Fusarium has two different types of spores. So, if it completes a sexual cycle that takes a
long time and probably happens throughout the winter in crop residues that were left on the
surface of the farm, it will then release these airborne spores at the start of the season. And

(07:32):
those can travel very long distances and can land on a crop very far away. And if
that crop is flowering, then that is when it has its opportunity to get into the plant.
Once inside those plants, it then goes through a more quicker infection cycle, and it then can
produce genetically similar asexual spores. And they are rain splashed throughout a crop.

(07:58):
So, you can see the disease cycle starts with the wind blowing in spores. And once within
a field it'll be splash transmitted by the English summer’s rain throughout the crop.
So that must be pretty difficult to control, because if these spores are windblown, presumably
very long distances, it must be incredibly difficult to control that sort of thing.

(08:24):
So, if we focus on wheat as an example, we do have wheat cultivars that are partially resistant
to Fusarium. So that means the Fusarium can get in and destroy a single bunch of flowers rather
than spread throughout the entire plant. And it does reduce the amount of infection. However,

(08:47):
it doesn't stop the problem of the mycotoxins and their ability to spread throughout the plant.
If you get four infected heads in the area of a football pitch of a cereal field, that's maybe
enough to make you fail the mycotoxins test. So, the level of control required is very high.

(09:10):
We spray fungicides on to our crops to protect them from diverse fungal pathogens. They are
partially effective, but Fusarium has some extra copies of the target for the commonly used
fungicides. So, it's intrinsically more resistant than some other pathogens. And sublethal doses of

(09:33):
these fungicides can actually stress out the fungus a bit and make it produce more toxins.
So, are there any other negative effects?So, beyond the farm, Fusarium also cause
problems in hospitals. So, the W.H.O released a list of high priority pathogens for fungi,

(09:55):
of which Aspergillus and Candida species are in the top critical category. Fusarium are an
emerging category under the high priority list because of their drug resistance and because
of that increasingly being detected in people.It's generally a waterborne source of infection,

(10:17):
so you might have a contaminated contact lens solution, and you get an infection of your cornea,
which might require a cornea transplant. Or you are unfortunately infected during some
medical procedure, and you've obtained Fusarium inside you, and then you could get some invasive
Fusariosis. And that can be highly deadly.You've just mentioned the Aspergillus as well

(10:45):
with the World Health Organization because that's another one you're
working on. So, tell me about that?So, Fusarium and Aspergillus are everywhere,
they're in our urban and farming environments. The Aspergillus would be, I've got a mouldy
environment, I've breathed in these airborne spores, I therefore get pulmonary infections.

(11:07):
If you are immunocompromised or you have cystic fibrosis or Covid, then you're more prone for
that to deteriorate into an invasive disease that are difficult to control, whereas the Fusarium are
more acquired by those dirty solutions.Right. So, what are you looking at with
Aspergillus? What are you wanting to find out?Well, for both Aspergillus and Fusarium,

(11:29):
we're interested in how they are adapting to the changing environments in our farm settings.
So, we are doing less ploughing to improve our soil health. So, this means we have
more organic matter on the surface of our farms.We are using more irrigation and agrochemicals,

(11:52):
so we're applying more solutions to our soils. Our soils are therefore becoming more salty,
more acidic, and more contaminated with some of these agrochemicals, including the fungicide.
So, we're interested in how both of these groups of fungi are adapting to those stresses. And if

(12:13):
those stresses alone can make our drugs less effective in clinics because people have shown
in Aspergillus that horticultural waste that is rich in fungicides can promote the evolution of
resistance to drugs that then causes problems for treating people with Aspergillus in hospitals.

(12:35):
So, at the core of your research is essentially trying to understand,
like how are they getting into the plant? That's the core of your research with Fusarium, isn't it?
I really like to understand how fungi sense their environment. So how do they decide, I am now on
a plant and I'm going to turn on my toxins, because in the lab, it's actually very hard to

(12:59):
make them make toxins, you have to trick them. They don't produce these things all the time.
So, what are the environmental cues withinside a plant that goes right,
I'm hungry, I need to make some toxins to get some food. And it's about understanding those
triggers. Because if we can understand what turns the fungus toxins on, can we develop non-lethal

(13:22):
drugs that turn the fungus’s toxins off and therefore protect our food security a bit more?
So how are you studying this?So, in our lab we do a lot of
genetic engineering. So, we might identify an interesting group of proteins that we hypothesize

(13:44):
are important for sensing environments. And then we can create mutants of these
fungi that lack individual proteins. And then we can quantify the amount of disease they cause,
the amount of mycotoxins they can produce. We can look at where they are inside a plant if we can
tag them with fluorescent proteins. Or it might be that we've done some transcriptomic experiment,

(14:11):
and we've looked at what genes are being expressed inside the plant at specific points,
particularly at the start of infection when toxins are high. And then you can
identify genes that are more likely to be involved, and then you might use those as targets.
So, we've been chatting about this all the way along, but how can you apply this knowledge? I

(14:35):
mean you can instantly see, I think talking to you what the ramifications are as you start to
understand how the fungi infect plants.So, I think we've got two strategies
for trying to make a difference in different durations. So, identifying and understanding

(14:56):
how Fusarium regulates mycotoxins during infection is probably a long game.
So here you're going to identify pathways that are important. But you don't know if all of these
targets are actually druggable or feasible. Because as we discussed at the start, fungi
are actually more closely related to animals than they are plants. So, the vast majority of targets in

(15:21):
a fungus are not druggable in a fungicide way, because they could have a negative effect on us.
So, you wouldn't want to spray that on your food.And then we are looking at proteins that are on
the surface of the fungus. So, they’re accessible to a drug particularly like
the receptors. So, we've done some work on G protein-coupled receptors,

(15:42):
which are like the things that we have on our tongue for sensing taste, in a fungus. There,
there is some unique specificity to specific fungi that wouldn't have cross-reactivity with humans,
but that's a long drug discovery kind of pipeline.For having a more immediate impact. We're looking

(16:03):
at harnessing the power of the microbiome and nature to our advantage. So, we've got
some wild yeasts that can inhibit Fusarium from growing, and we're trying to adapt those yeasts
to actually help us decontaminate cereals that have already been infected with Fusarium. So,

(16:27):
we can hopefully make safer animal feed.So, we're talking about food security here,
that's pretty big, I'm guessing, is it well supported, the research that you do?
So comparatively with clinical research, the amount of funding that goes into food security

(16:49):
research is a fraction of the funding, and it is a significant problem. And I do
believe that situation has somewhat deteriorated post-Covid. People are very concerned, rightly,
for the impact of new infectious diseases in people and the growing problems of other genetic

(17:10):
disorders and direct impacts on human health.But the biggest determinant of human health is
the food that we eat. And if we do not protect that source, we are all vulnerable to disease.
The amount of food that we lose to fungal diseases is only ever increasing. As our climates change,

(17:32):
we are getting the evolution of new fungal diseases and the spread of existing fungal
diseases into new areas, that are then coming into contact with new crops, and then that is the
biggest driver of having new disease outbreaks that our systems are not in place to protect.

(17:52):
So, why is understanding evolution so important for you, do you think?
So, for predicting what might happen in the future and how we are going to be able
to control these pathogens of people and plants, we need to understand how they're

(18:12):
going to evolve and adapt to the changing world. And if we don't understand that,
we are going to get surprised by these pathogens and what might come. And that worries me.
We've all seen ‘The last of Us,’ I'm glad it made fungi cool for a year
or two. But that opening scene with the doctor explaining what will happen if fungi all adapt

(18:37):
to 37 degrees and they'll all infect us, is a worrying situation, that isn't too far-fetched.
Neil, thank you so much for talking with me.This was a podcast by the Milner Centre for
Evolution at the University of Bath. I'm Turi King and thank you for listening. If you have

(18:57):
any thoughts or comments on this or any other episodes, please contact us through social
media. For more information about the Milner Centre for Evolution, you can visit our website.