How do fungal diseases infect our bodies?

We currently have only a very limited repertoire of drugs with which to combat fungal infections. This is partly because fungal cells are so similar to our own, so it’s harder to identify differences between the two that drugs can exploit. But that’s the goal now: to better understand the mechanisms by which these organisms invade the body and become virulent. This will help to highlight potential targets for novel drug development. It’s what Carolina Coelho is doing at the University of Exeter…

Carolina - If we understand how they get into our bodies, if we identify certain molecules—which are kind of the chemical points of entry—we can try to block them. We can try to decrease them with drugs. We can try to create vaccines. Fungi are really interesting because they're masterminds of chemical manipulation. If we understand better these chemical manipulations that they carry out in our bodies, we can fight the disease. But the other interesting thing is that every time we understand these chemicals better, a lot of the time we find alternative uses for them. So many of the chemicals that fungi produce are, for example, used in modern medicine. Things like penicillin, cyclosporin, and the drugs that lower cholesterol—which millions of people worldwide take, the statins—are all derived from chemicals that fungi produce naturally, and that we were able to hijack for our medicine.

Chris - How do they actually get in though? Because that's the crucial question. How do we track down the route into the body that these organisms take?

Carolina - Mostly, we know where they are present in the environment—at least the ones that cause important diseases. We know, for example, Cryptococcus, cryptococci, exist in the environment. And we have clues from many different systems. For example, we know that koalas tend to have nose infections with cryptococci, and we know cryptococci are on the leaves. So then we can identify the anatomical place of entry—we think it's inhalation. For example, with Candida, we know that it exists on the skin of most people, and it also exists in our guts. So actually, Candida already exists in our bodies. Now, what happens is, due to some change—usually when the host, the human, is a little less healthy—it creates an imbalance in the system, and then they can really start to create havoc. So, for example, Candida will start leaving the gut and getting into the bloodstream. Candida should only be in the gut. In any other organ—like the heart or the bloodstream—it will cause a huge amount of problems.

Chris - If we look at the fungus—if we look at, say, a Candida cell—when it's being pathological compared to when it's just sitting harmlessly in our guts or skin, kept in check, does it look different?

Carolina - Yes, absolutely. The Candida in our gut tends to be round—it looks like an egg. We describe it as an egg. But again, once that imbalance happens, it can form what we call a hypha. A hypha is a tube. This tube is so strong that it can literally pierce through our tissues. It's also much harder to treat because it becomes larger than our immune cells. If you're trying to fight an enemy that's physically bigger than you, that becomes difficult. So you need a different array of weapons in our immune system. And with Aspergillus, which is associated with serious infections but is also a trigger for asthma—when we grow it in the lab (and you’ve all seen Aspergillus growing on oranges), we have to seal everything. It can lift the lid off certain plastics. That’s how strong the fungal growth is.

Chris - If we can see that the fungus puts itself into an aggressive mode—it’s like a dog with its lips drawn back and its teeth bared—if that’s the active form, and we can work out how it’s doing that, then presumably that discloses a vulnerability? So that’s how we attack it—we detect when it’s in that form and strike while it’s vulnerable. That gives us a way of stopping it.

Carolina - Absolutely. That’s precisely what the centre is trying to do, and what all the other medical mycologists are working on. For example, if we can block a certain chemical from being produced, or if we can make a vaccine that binds to and blocks that chemical—absolutely.
That’s something we’re really trying to work out. We could try to develop drugs to block it. And again, sometimes that chemical is useful in other contexts. What it does during a fungal disease might be useful elsewhere. For example, Cryptococci are coated in a sugar capsule that makes them invisible to the immune system. Once we know the structure, we can create a vaccine to target it.