Every zombie movie has its own explanation for the apocalypse. In the currently successful HBO series “The Last of Us” it is a mutated fungal pathogen that turns people into zombies. Oliver Kurzai knows just how threatening fungi really are for people and what opportunities they offer medicine.
SZ: As an expert on fungal diseases, do you immediately look at “The Last of Us”?
Oliver Kurzai: I haven’t seen the series, but there’s a lot of talk about it in my field now. That’s why I watched at least excerpts.
What is this zombie mushroom scenario all about?
The fungus that becomes a pandemic pathogen there is based on a real biological example, viz Ophiocordyceps unilateralis. This fungus is capable of infecting ants and causing them to undergo complex behavioral changes.
In the series, this is transferred to humans …
… and very exaggerated to the extreme. This fungus cannot even affect all ants on this planet, but only a few specific species. And for it to suddenly do the same thing in humans, there are too many barriers for that.
Oliver Kurzai is head of the Institute for Hygiene and Microbiology at the University Hospital Würzburg and head of the National Reference Center for Invasive Fungal Infections at the Leibniz Institute for Natural Product Research and Infection Biology in Jena.
(Photo: Daniel Peter/University of Würzburg)
What barriers?
For example, the fact that humans are chemically different from ants. Or the body temperature in humans: 37 degrees is anything but a comfortable temperature for most fungi. You can no longer grow there. There are also mechanisms in our immune system that are specifically directed against fungi.
So the plot of “The Last of Us” remains fiction.
Yes, fortunately.
Nevertheless, when watching the series, one wonders whether the next pandemic could be a fungal disease.
Probably not in the sense of a pandemic like the one we’ve just experienced. In fact, we have been observing for about 25 years that new fungal pathogens are spreading worldwide. An important example is White ears. It was first found in 1996 and scientifically described in 2009. Back then, nobody knew that this fungus would actually start to spread globally. Then he performed in India, in Asia, suddenly he was in South Africa, in the USA. There is now White ears worldwide, and still no one knows where the fungus came from and how it made the leap to infecting people in multiple places around the world at the same time. We are monitoring this situation closely because the fungus has two properties that make it dangerous: It is relatively resistant to drugs. And it can be transmitted from patient to patient quite effectively. It’s an awkward combination.
That sounds a lot like a second version of the corona pandemic.
But there are fundamental differences to a virus pandemic: The first is the speed of spread. This fungus has been working for many years now to spread worldwide, such a coronavirus makes it within a few weeks. Then the number of people affected is also much lower, because only certain people at risk get sick from this fungus. Invasive fungal infections will never have such high numbers of diseases as with Covid. The third difference is that the virus pandemic will eventually go away, while we have to assume that a fungus will stay. We are not aware of a herd immunity in fungi that leads to the infections being milder or no longer clinically relevant.
“In research, mushrooms often fall off the back. That could fall on our feet at some point.”
What can invasive fungal infections do to the body?
There is a wide range of clinical pictures. The mold Aspergillus about every one of us breathes in daily because the spores are everywhere. For healthy people, it is usually completely harmless. But when patients with a weakened immune system inhale this fungus, it can colonize the lungs and cause a serious invasive lung infection. Starting from the lungs, the fungus can then spread throughout the body. Another prominent example is Candida albicans, a fungus that typically lives in the human intestine and doesn’t actually cause any problems there. However, if the immune system is no longer functioning, the fungus can enter the body via the intestinal mucosa, trigger a type of blood poisoning and spread to the internal organs.
Despite such clinical pictures, most people hardly think about fungal infections, at most about athlete’s foot or nail fungus. Should people be more aware of fungal diseases?
In fact, fungal infections have always had a niche existence – wrongly so, in my opinion. Mushrooms often fall behind in research, politics and science funding. There is currently only one medical microbiology department in the whole country that deals with fungi. That could come our way at some point. Because invasive fungal infections are increasing.
How can this be explained?
Presumably because the number of patients whose immune system is no longer working properly is increasing. people get older. Organ transplants, treatments such as toxic chemotherapy, and longer periods of treatment in intensive care units are increasing. The immune system of such patients no longer functions properly and the risk of an invasive fungal infection increases.
Is there no vaccine against fungal infections?
None approved for humans. Vaccines are currently being developed for some pathogens. But for some it’s not that easy. For example with the pathogen already mentioned Candida albicans, which lives in the intestines of healthy people. If we were to vaccinate against this pathogen now, what would actually happen to the intestinal flora? In addition, the people who become seriously ill are those whose immune systems no longer function. Vaccination doesn’t work properly for them either.
“Fungi make active substances that a chemist cannot even imagine.”
How can you still protect yourself against fungal diseases?
I advise vaccination against other diseases. For example against pneumococci, meningococci, but also against the corona virus or the flu.
How does that keep the fungus away?
This reduces the risk of a secondary fungal infection. For example, if I got so badly ill with the flu that I had to be treated in the intensive care unit, then I have a high risk of a fungal infection. The flu shot also provides some protection against the fungus.
But there are at least effective drugs against fungi.
Yes, there are essentially three to four classes of antifungal drugs that we can use to treat it. And when I started my subject, I still learned that fungi do not develop resistance. That was a total misjudgment – they do it, albeit much more slowly than bacteria. But it means we have a problem when a pathogen develops resistance to any of these antifungal classes. Then a substantial part of the treatment options are lost. Unfortunately, we see such cases again and again.
Is there a chance of new drugs?
There are a few that are in the pipeline and also badly needed. There are some substances with fundamentally new mechanisms of action.
Where can such substances be obtained, for example?
One class of substances we use to treat are natural products, ironically made by fungi. So there’s one fungus able to make a substance that kills another fungus, probably to have a competitive advantage in the ecological niche.
Mushrooms can also bring benefits to medicine.
Mushrooms are incredibly diverse. And many are very good producers of substances that serve all sorts of biological purposes. Mushrooms make active substances that a chemist cannot even imagine. You can think of fungi as a chemical miracle library.
Which active substances do we have to thank mushrooms for?
For example, the antibiotic penicillin or lipid-lowering drugs, which are given for cardiovascular diseases, and active ingredients that inhibit the immune system and are used in transplantations or multiple sclerosis – all these are substances that come from fungi. An incredible treasure. And we are only just beginning to understand its diversity and enormous complexity. I do have hope that, thanks to mushrooms, we will find many more active ingredients that will help us advance in medicine.