Which diseases do fungi cause?

When we think of infections, viruses and bacteria usually come to mind first - not fungi. But as we heard in our previous recent foray into the world of fungi, fungal infections caused 2 million deaths in 2020. And that was a year when much of the world was staying indoors and away from one another to fight off Covid-19! Indeed, viruses and bacteria have hogged the infection limelight for the majority of the time that microbiology has existed as a discipline. But this is changing; and multiple wake-up calls in the form of novel and emerging fungal threats causing human, animal and plant diseases, as well as a rising tide of resistance against our - currently - limited repertoire of antifungal drugs mean that scientists are now sounding the alarm. And, in partnership with the Wellcome Trust, in this follow episode on fungi we’re diving into what the threats are, why this is happening, and what needs to be done - urgently - to ward off the risk. To kick off, where are fungi making their presence felt? Wellcome’s Senior Research Manager, Sumi Robson…

Sumi - They can cause everything from really mild superficial infections—we've all heard of athlete's foot—but they can also cause much more severe infections, particularly when they become invasive. So if they get into your bloodstream and cause bloodstream infections, Candida, which causes thrush if it's in your mouth or in the vaginal tract, can cause a bloodstream infection if it gets into your bloodstream, and that can be really severe.

Chris - Why is it that they can have that range of being trivial right through to really severe, and is that changing?

Sumi - Fungi, in a way, are opportunistic. Our body has a really good defence system—our immune system is great—but when it's weakened in different ways, that's when fungi can really take a foothold. So "weakened" can be just a bit run-down—that’s sometimes when we get fungal infections—but we really see it in patients with HIV and AIDS, people who are having chemotherapy or radiotherapy. But actually, increasingly, we're seeing it in people with more chronic conditions—diabetes, chronic lung disease, or liver disease—those sorts of conditions where the body's just a bit run-down all the time, and the fungi have the opportunity and take a foothold.

Chris - Are we in good shape in terms of being able to treat it, though? I mean, if it was a bacterial infection, we are—although we're worried about antimicrobial resistance, we still have quite a deep bench of drugs to fall back on. Can I say the same for fungal infection?

Sumi - In a word, no. We only have four types of antifungal drugs, which target different pathways within the fungus, and we're seeing increasing resistance to those as well. Probably most worrying is that we've seen a new pathogen emerge called Candida auris, which is what we call intrinsically resistant—or it was born resistant—to a couple of the drugs, which means really we don't have much to fall back on at all.

Chris - Why is that? Why has there been a relative paucity of antifungals, but we've got loads of antimicrobials of other kinds?

Sumi - I think two main reasons. Firstly, fungi are just overlooked and understudied across the board, right? They just haven't been invested in the way we have other pathogens. But also the real challenge with fungi is that they are so similar to us, which is great in some ways in that we can use them to study humans, but it means that if you find a drug that targets a fungus, it's quite likely that the protein or the molecule it targets—we've got something really similar in us.
So when we take those drugs, it causes side effects, and so finding a drug that kills the fungus without the side effects is really challenging.

Chris - Are there any areas of the world that we should particularly concentrate on that might be hotspots for this sort of thing happening? Because one of the things we've seen time and time again with the emergence of disease is that these sorts of emerging infections do not need passports—they don't obey geographical barriers—they go where the people go, they go where the wind goes. So are there areas we need to keep an eye on, knowing that they might be the breeding ground and the origin, and then all of us are vulnerable?

Sumi - I think it's generally where we find vulnerable populations, particularly vulnerable populations living close together, particularly in harsher conditions. So I think humanitarian settings are somewhere we should really keep an eye on. But again, I think one of the challenges with fungi is that we don't really do any disease monitoring, so we don't know how many fungal infections are happening worldwide on a daily or annual basis.
You know how every flu season we know roughly what flu strains we're likely to see, and with COVID we were all very familiar with constant disease tracking—but that doesn't happen at all for fungi. So we don't really know what fungal pathogens might be happening.

Chris - And is that something you think needs to change? Is that something, for instance, a funder like the Wellcome Trust even, should be saying, "This is what we need. We need some kind of map, supported by genetic codes and so on, so we can keep tabs on who's got what and where"?

Sumi - Absolutely. I think especially for those pathogens—fungal pathogens—that we think are on the rise, we really need to be keeping a closer eye on them and linking it really closely to climate data, so that we can see, as fungi are adapting to climate change and as the climate is changing, are we seeing changes? Are we seeing differences? And where are those differences happening? Which populations are they affecting more? So that we can then go in with suitable interventions.