Isaria cicadae

Isaria cicadae is an ascomycete fungus that parasitizes cicada larvae. It forms white and yellow asexual fruiting structures resembling synnema. While mostly being found throughout Asia in warm, humid regions, it has been found on various other continents. It is known in Traditional Chinese Medicine as Chan Hua and commonly called “cicada flower.” Its medicinal uses date back to the fifth century AD in China. It can also be used in various foods and tonics.

Taxonomy
Isaria cicadae is thought to be a cryptic species because of how many different species names have been attributed to it and the controversy over what the correct species name is. I. cicadae was originally described as Isaria cicadae Miq. by Miquel in 1838 until he synonymized it with C. cicadae in 1895. Paecilomyces cicadae was synonymized with C. cicadae in 1974 by Samson. Soon after, S.Z. Shing described the species again as Cordyceps cicadae Shing in 1975, but these are all thought to be generally synonymous. C. cicadae and I. cicadae are both often used in the literature. I. cicadae is thought to be the most current name for the species, although the true taxonomy is still in flux. Other reported synonyms include Cordyceps zhejiangensis , C. sobolifera, C. sinclairii .

Description
Isaria cicadae forms its fruiting structures on the surface of its host, a cicada nymph. The fruiting structure can either cover the entire nymph body or only partially cover it. Sexual structures are not produced on these fruiting structures. Much more information is known about the asexual morph of this fungus because the sexual morph has been reportedly observed once in nature and never in the lab. Its asexual fruiting structures are synnema-like and produce conidiophores and conidia. The fruiting bodies have yellow stalk-looking structures with a white-ish, fluffy tip where the conidiophores are located.

Ecology
Isaria cicadae is an entomogenous fungi that parasitizes the nymphs of its cicada hosts and forms fruiting structures on the surface. These fruiting structures are produced from June–August, and they protrude from the nymph, up through the soil after the fungus kills it. Asexual means of reproduction occur once temperatures rise following sclerotium development and is done so through conidia, dispersed by air and water. It is said that this fungal species is rare and scarce because it propagates slowly and lacks resistance. This could also be due to the fact that it is largely asexual and clonal in nature, as sexual structures have yet to be reliably observed in lab or in nature. Despite this, there is evidence supporting that it is heterothallic being that a study found a truncated MAT1-1-1 type found in the MAT1-2 locus that is not due to asexual fruiting.

Its genome has been sequenced and found to be 33.9Mb including serine proteases and chintinases which target host tissues and are characteristic of other entomopathogenic fungi. The fungus also produces metabolites such as beauvericins and oosporein which have non-selective insecticidal properties. This would suggest that the fungus could infect more than one host, but this has only been seen in the lab on silkworm pupae and beetle wings.

Life cycle
The life cycle of Cordyceps cicadae (synonymous with I. cicadae) in southern China as observed and described by Zha, Ling-Sheng et al. in 2019 follows. During mid-late summer, conidia of I. cicadae attach to the surface of a cicada nymph’s body within the soil which germinate and form germ tubes that can penetrate below the surface and form hyphae. After two to three days of absorbing the cicada’s nutrients and reproducing, they can occupy the entire body. Hyphae turn to mycelia which cause the nymph to die from absorbing water and nutrients and producing mycotoxins. After the nymph is killed, the fungus forms a sclerotium and produce antibiotics to keep the body from rotting. When temperatures rise again, either that year or the following, mycelia are produced once more to form synnemata that eventually break through the soil to grow above ground. The synnema branches to form multiple conidiophores and chained conidia. The conidia are dispersed by air or water, leading them back to the soil, where they use water flow to infiltrate the soil until they make contact with another nymph and infect.

Habitat and distribution
Isaria cicadae is found in warm, humid, low-elevational regions (below 2,500m), on cicada nymphs in sunny soils. Habitats that fit these criteria include bamboo, broad-leaved, coniferous, and broad-leaved mixed forests. They are mostly found in China, but have also been found throughout Asia, Europe, and North America, with some studies showing other continents as well.

Medicinal properties
''Isaria cicadae/C. cicadae'' is one of the oldest, most valued and well-known forms of Traditional Chinese Medicine, dating back to the fifth century AD. When used as a medicine, it is referred to as Chan Hua. Many of its medicinal properties relate it to the more commonly used Cordyceps sinensis and Cordyceps militaris, making it a potential substitute for these highly sought after medicinal fungi. Obstacles to using I. cicadae on a larger scale alongside its relatives C. sinensis and C. militaris include its scarcity and its cryptic taxonomy which make it difficult to study, cultivate, and harvest. It has been shown to be helpful for a multitude of health issues and concerns and nonsignificant toxicity has been reported meaning it is thought to be safe to use as treatment. On the other hand, oosporein, which is produced by the fungus, has been shown to cause issues in some species including birds and chickens, canines. Oxalic acid also produced by the fungus could be cause for kidney stone disease in high levels.

Putative active functions

 * Treatment of childhood convulsion
 * Analgesic activity and sedative function
 * Anti-fatigue effects
 * Antitumor activity
 * Amelioration of renal function
 * Immunomodulatory effects
 * Immunoregulatory

Medicinal uses and treatments

 * Malaria
 * Palpitations
 * Cancer
 * Fever
 * Diabetes
 * Eye diseases
 * Dizziness
 * Chronic kidney diseases
 * Acute conjunctivitis
 * Chronic blepharitis, dacryocystitis, and pterygium

Other uses

 * Improving eyesight, removing eye cloudiness
 * Neuroprotection
 * Promoting eruption
 * Liver and kidney protection
 * Blood fat reduction

Chemical constituents
Chemicals isolated from I. cicadae/ C. cicadae include nucleotides and nucleosides, sterols (ergosterol, mannitol), cyclic dipeptides, sugars, polysaccharides, fatty acids, amino acids, aromatic compounds, galactomannan, adenosine, uridine, inosine, guanosine, cyclopeptides, myriocin, and inorganic elements.