Humans have made big leaps in technology over the years. The first mobile phone was made nearly fifty years ago, which isn’t a long time in the grand scheme of things. We’ve sent people into space and explored the deepest oceans, but there’s another world that still holds many secrets.
The kingdom of the microscopic is fascinating; you’d be surprised how much activity goes on in a bacterial or fungal cell. Our medicines and treatments often come from these humble sources.
What springs to mind when you think ‘fungi’? Probably something not suitable for talk around the dinner table!
There is a common misconception that fungi are like bacteria, when in fact they have their own biological kingdom of organisms. They are eukaryotic, like us, whereas bacteria are single-celled prokaryotes.
A eukaryotic cell has a clearly defined nucleus that is wrapped in a nuclear membrane. Prokaryotic cells lack this and other internal membranes.
The fungi kingdom is very old, over a billion years! As complex organisms, fungi have an abundance of activity inside their cells. They also have their own biochemical mechanisms to ensure their own survival, like what our immune system does for us.
Through serendipitous and measured research, fungi have been recognised as pretty good sources for mining potential drug leads. Many medicines are made from fungi or have fungal precursors in drug development.
Let’s take a look at three important discoveries:
Penicillin—the birth of the modern antibiotic
Antibiotics are big business. In 2020, the global market value of antibiotics was valued at over $40 billion USD. But these compounds weren’t always manufactured in cold, sterile laboratories.
Both bacteria and fungi produce antibiotics. These biochemical substances stop the growth of other bacteria that compete in the same environment.
Unless you’re allergic to it, you’ve most likely had a course of penicillin before. This wonder drug revolutionised surgical aftercare and allowed us to treat infections that could turn fatal without medical care.
In 1928, a Scottish physician named Alexander Fleming left a dish of Staphylococcus aureus, a type of bacteria, on his workshop bench. After returning from a holiday, he observed some mould (i.e. fungi) that grew on the dish. The area that surrounded the mould had no bacterial growth.
Something had stopped the bacteria from spreading across the whole dish, and very effectively. But what was it?
It was later found that this fungal mould, Penicillium notatum, produced penicillin. Though Fleming made the initial discovery, it took a major effort to bring the antibiotic to the first patient. It wasn’t until 1945 that penicillin was readily available in pharmacies.
Penicillin works by inhibiting the synthesis of the bacterial cell wall. This means bacteria can’t form properly, so they die. Nowadays, we have many different antibiotics that are based on the initial compound, including amoxicillin, flucloxacillin and phenoxymethylpenicillin.
This discovery also gave way to a whole group of life-saving drugs called beta-lactam antibiotics, which include all the penicillins, carbapenems, and cephalosporins.
This discovery is often the most well-known account of fungi used in medicine. From this accidental discovery of an antibiotic, fungi undoubtedly led to many lives being saved from severe infections.
Statins—for cholesterol and beyond
Statins often got a lot of bad press, despite their proven usefulness.
A constant stream of half-truths in the media can easily prey on your fear of medication side effects. Rest assured, statins are here to stay. They are one of the most effective ways of reducing the risk of cardiovascular disease (apart from having a good diet and regular exercise). Many clinical trials demonstrate the effectiveness of statins.
Statins, however, are not drugs that were cobbled together in a lab. They originate as compounds produced by fungi.
In 1976, Dr Akira Endo published a paper discussing the discovery of a new substance that inhibited cholesterol synthesis. This discovery took many years of work, 6,000 fungal broths, and a small team of researchers in Tokyo.
Eventually, Dr Endo’s team found a compound that blocked an enzyme involved in cholesterol synthesis called mevastatin. The clever bit of science that Dr Endo employed was in understanding how useful fungi are as a source. In his paper, he explains how previous research had shown that another fungal antibiotic called citrinin showed cholesterol-lowering effects in rat liver.
The fungi that produced mevastatin? Penicillium citrinum. From the name, you might guess that it grows as a mould on citrus fruits.
But don’t go eating that mouldy orange now!
Cyclosporin—the wonders of immunosuppression
When a new organ is transplanted there is a risk of the individual’s body rejecting the new tissue. Our immune systems are primed to recognise even the smallest molecules as ‘non-self’ before attacking. This means putting an entire, foreign organ inside your body is very risky.
We need to suppress the immune system and allow the new organ to settle into the host’s body without rejection, which is where medicines come in.
Cyclosporin originally came from the fungi Tolypocladium inflatum, in 1969 in a bag of soil in Switzerland. It wasn’t until 1976 that the immunosuppressant effects of the drug came to light, as it was previously thought to be a potential antibiotic.
In the past, corticosteroids and azathioprine, another immunosuppressant, was used in post-transplant patients. Azathioprine, however, brought with it side effects that affected the bone marrow. Transplant teams needed another, more palatable drug for their patients.
Some of your bones have spongy tissue inside them called bone marrow. It produces cells that mature into red blood cells, white blood cells, or platelets.
The discovery of cyclosporin gave way to a new generation of immunosuppressants: calcineurin-inhibitors. Calcineurin is a substance that activates the immune system’s T-cells, a type of white blood cell. By inhibiting this, the immune system is ‘calmed down’, and transplant organs can settle into the patient’s body. Despite not affecting bone marrow, cyclosporin can cause toxicity in the kidneys.
It is puzzling to think why fungi produce an immunosuppressant-type compound. Perhaps future research will solve this mystery for us!
Fungi—an important source for a cure
We’ve covered three different drugs, but there are many more medicines that fungi have either produced or contributed to the development of. Though fungi can be a source of infection, they can be a source for a cure. In the growing body of COVID-19 research, there are some interesting studies to show the potential for fungal metabolites that provide anti-COVID-19 substances.
Fungi have an important role in medicine, and nature as a whole is a fantastic source of healing. It simply requires us to invest some patience and effort in engaging with it.
Disclaimer: The information in this post is for educational purposes only. For medical advice, please consult your GP or another appropriate clinical practitioner.
