Researchers cultivate a very powerful “zombie fungus” in the laboratory

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You may know the Cordyceps mushroom like “zombie mushroom” – for good reason. Its name is derived from Greek and Latin, meaning “clubhead”, and many nature documentaries have focused on its frightening ability to infect certain insects, notably ants, and literally hijack their bodies. Cordyceps evolved alongside these ants and made them an incredibly complex and macabre part of its reproductive cycle.

Most of us wouldn’t usually think of mushrooms as particularly clever, but Cordyceps is a great window into how little we understand about mushrooms. When a bachelor Ophiocordyceps unilateralis spore infects an ant, it begins to travel in its blood, multiplying. Before long, these individual cells begin to work in concert, linking via tubular hyphal protrusions to begin communicating and sharing nutrients.

These fungal hyphae then begin to spread through the ant’s muscles, penetrating and encircling muscle fibers throughout the ant’s body, with one notable exception. Unlike science fiction zombies, Cordyceps usually leaves the ants’ brains completely intact. Instead, acting like a superorganism, the fungal network begins to strangle the ant’s motor neurons until the ant’s perfectly intact brain is more or less totally isolated from its body.

A “zombie ant” infected, controlled and eventually consumed by Ophiocordyceps unilateralis

If the process seems incredible so far, what happens next is truly frightening. The fungus takes over the ant’s body and begins to “drive” it like you or I might a car. Ant locomotion systems are relatively simplistic, and Cordyceps learned over the eons how to operate the legs. That would be a feat on its own, but the fungus also knows exactly where it wants its host to go next.

It prompts the ant to find a vertical plant shoot or a tree trunk to climb, close to the ant nest. It pushes the ant about 25 cm (10 in) up the plant where the temperature and humidity are most appropriate. And that causes the ant to bite into the central stem of a leaf, putting its jaw into a deadly lock and determining the ant’s final resting place.

There’s no way to tell what the ant’s isolated brain undergoes through this process, but over the next few weeks its body will be consumed by Cordycepsand its head will burst as the mushroom’s reproductive organs burst into a phallic protrusion that will eventually swell a fresh batch of fungal spores, which gently float to the forest floor, the perfect height, not far from a nest of ants, ready to infect new victims.

So far Earth, and so The last of us. The terrifying fungal intelligence displayed by this ant-puppeteer organism makes exceptional fodder for documentary footage and science fiction. What many people don’t realize, however, is that it’s just a particularly horrific species of Cordyceps. Researchers know of more than 750 others, each of which bases its life cycle around a particular host – often insect larvae – with a process just as finely tuned as the one described above.

A wasp parasitized by the fungus Cordyceps
A wasp parasitized by fungus Cordyceps

What many Western countries also fail to realize is that certain types of Cordyceps mushrooms – especially Cordyceps militaris and Ophiocordyceps senensis – are premium health supplements in many Eastern medicinal traditions, where they have been used for centuries to treat fatigue, kidney disease, low libido, respiratory problems, high blood sugar and a range of other conditions. There has been a number of scientific investigations into the effects of these fungi and their chemical constituents in animal and laboratory models, and some results have certainly looked promising.

“Its extracts and bioactive constituents,” reads a 2021 review of peer-reviewed research in the journal Frontiers in pharmacology, “have been linked to the production of cytokines such as interleukin and tumor necrosis factor (TNF)-α, stimulation of immune cell phagocytosis, nitric oxide production by increasing the inducible activity of nitric oxide synthase and stimulation of inflammatory response via mitogen-activated protein kinase pathway.Other pharmacological activities such as antioxidant, anticancer, antihyperlipidemic, antidiabetic, antifatigue, antiaging, cholesterol lowering, hypotensive, vasorelaxant, antidepressant, aphrodisiac and renal protection have been reported in preclinical studies.

Its popularity as a health, energy, immune system and stamina supplement, combined with a complex reproductive process that relies on other organisms, has made Cordyceps extremely expensive. And while lab-grown “vegetarian” Cordyceps CS-4 extracts are widely available commercially as affordable (and largely unregulated) health tonics, they are usually grown on fermented rice grains.

Wild Ophiocordyceps sinensis;  a very expensive traditional Chinese medicine.  You can see the shape of the larva that each mushroom consumed, as well as the fruiting body protruding from where the insect's head once was.
Ophiocordyceps sinensis wild; a very expensive traditional Chinese medicine. You can see the shape of the larva that each mushroom consumed, as well as the fruiting body protruding from where the insect’s head once was.

The problem, according to researchers at the Korean National University in Chungbuk, is that putting Cordyceps on this type of vegan diet results in an inferior product, with particularly low levels of a key bioactive compound called cordycepin, which researchers consider to be the significant “therapeutic” component.

The team therefore sought to determine whether the cultivation of a cultivated strain of Cordyceps militaris in the laboratory on an insect-based substrate instead of rice would increase its levels of useful cordycepin. The team collected six different types of commercially available dried insects, all approved to be sold as food in Korea: crickets, silkworm pupae, mealworms, grasshoppers, white-spotted cockchafer larvae, and rhinoceros beetles. Japanese, with brown rice as a witness. Then they cultivated Cordyceps on them for two months, harvested the fruiting bodies of the fungus and analyzed each type to see how much cordycepin was produced.

The results were wildly varied, but all of the insect-based mushrooms produced significantly more cordycepin than the rice-fed ones. The worst performing insect, silkworm pupae, produced about three times more cordycepin than rice. The best, the Japanese rhinoceros beetle, produces about 100 times more than rice.

Korean researchers cultured Cordyceps on six different types of food-grade insects and found that they were able to dramatically increase cordycepin production in the resulting fungal growths.
Cultivated Korean scholars Cordyceps on six different types of food-grade insects, and found that they were able to dramatically increase cordycepin production in the resulting fungal growths

Chungbuk National University

The researchers managed to limit the main factor to the fat content of the insects, in particular to their level of oleic acid. When oleic acid was added to silkworm pupae, it enhanced cordycepin production by an impressive 50%.

“The cultivation method of Cordyceps suggested in this study will enable the production of cordycepin more efficiently and economically,” said Dr. Lee, lead author of a new research paper describing this work. “However, securing edible insects is not yet sufficient to scale up to industrial scale. It is also believed that more efficient production may be possible through the use of other insects, which needs to be demonstrated by further study.

The research is published in the peer-reviewed journal Frontiers in microbiology.

Source: Chungbuk National University

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