Cordyceps Cicadae
Classification
Higher order taxa
Kingdom: Fungi Phylum: Ascomycota Order: Hypocreales Class: Sordariomycetes Family: Cordycipitaceae Genus: Isaria Pers. Species: Cordyceps cicadae
Species
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NCBI: https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?command=show&mode=node&id=218633&lvl= |
Cordyceps cicadae
Description and significance
Cordyceps cicadae is a parasitic fungus that survives by infecting Cicadidae hosts throughout parts of China, specifically the subtropical monsoon zones of China like Western Hubei, Zhejiang, and Western Hunan [1]. C. cicadae, like many cordyceps fungi, is an obligate parasite of the Cicadidae larvae and nymphs [2]. C. cicadae is also valued for its diverse medicinal properties: traditional Chinese medicine used the body of parasitized cicadas and the fungi within crushed to a fine powder as an antioxidant and treatment for neuronal diseases, renal fibrosis, acute kidney injury, and prescribed as an anti-aging tonic [3]. In preclinical studies, C. cicadae extracts have helped modulate the human immune system, reduce inflammation and oxidative stress, and may help combat kidney fibrosis C. cicadae coexists with other parasitic bacteria like Pseudomonas, Serratia, which can enhance its ability to produce nucleosides and ergosterol derivatives [4].
Genome structure
The Cordyceps cicadae genome is about 34.6 million base pairs long, arranged on 9 chromosomes, and has a GC content of 52.65%. It includes 8,019 protein-coding genes, most of which are involved in metabolism, transport, and other essential cell processes. Many genes fall into large, well-defined families, including 1,830 P-loop NTP-hydrolase genes, 775 Rossmann-fold dehydrogenases, and 444 major facilitator superfamily (MFS) transporters, along with 596 transporters classified mainly as electrochemical-potential-driven–driven and primary active transporters. The fungus produces 542 carbohydrate-active enzyme (CAZyme) genes, including 267 glycoside hydrolases (GHs), 162 glycosyltransferases (GTs), 71 carbohydrate-binding modules (CBMs), 54 auxiliary-activity enzymes (AAs), and 24 carbohydrate esterases (CEs). These CAZymes support the fungus’s ability to degrade and use complex polysaccharides, which is central to breaking down insect tissues and plant-derived carbohydrates. The genome also contains 97 cytochrome P450 genes, including 33 E-class group I and 13 CYP52 genes, which aid in lipid and secondary metabolite production. C. cicadae carries several gene clusters for nonribosomal peptide synthase (NRPS) and polyketide synthase (PKS) pathways that create bioactive secondary metabolites, like oosporein and beauvericin, used for defense and used by humans for? medicinal purposes [4].
Cell structure and metabolic processes
Cordyceps cicadae is an entomopathogenic fungus that primarily infects the cicada species of Macrosemia pieli and Platypleura kaempferi species. After the fungus infects the host, an ascocarp forms and grows out of the host’s body. The asocarp is a sexual fruiting body commonly known as a “cicada flower”. Cordyceps cicadae’s vegetative cells consist mainly of mycelial hyphae that penetrate the tissues of its cicada hosts, eventually killing and colonizing the host’s body for the ascocarp to grow. C. cicadae hyphae are septate and produce JCH-a1, a polysaccharide that alters the thickness of the extracellular matrix around the hyphae. These polysaccharides show triple-helix conformations, a structural feature associated with fungal cell-wall stability and immune defense [5]. Additionally, the cell wall of C. cicadae is composed of chitin, beta-glucans, and mannan-modifying enzymes, which alter cell wall rigidity, porosity, surface charge, osmotic resilience, and cellular interactions [4]. External and internal tissues of the ascocarp are typically covered in diverse microbial communities, including bacteria and other fungi. These microbial communities can aid in biosynthesis, producing nutrients and contributing cofactors, which can all benefit ascocarp growth and support cell wall development [6]. Cordyceps cicadae functions as a chemoorganoheterotroph, relying on organic molecules (protein, lipids, and polysaccharides) obtained from its insect hosts for energy and carbon sources. The fungus gains nutrients through metabolizing the host’s liver, adipose tissue, hemolymph, muscle tissue, and exoskeleton. To parasitize and metabolize the host’s carcass, the fungus produces enzymes such as s proteases, lipases, glycosidases, metalloproteases, and chitinases. Chitinases degrade the cicadae exoskeleton so hyphae can penetrate and extract nutrients. Serine proteases and metalloproteases break down circulating hemolymph proteins to provide amino acids to the fungus. Lipases and proteases digest stored lipids within the host to provide energy to the fungus. Glycosidases degrade the connective tissues, internal organs, and nervous system of the infected host [4[#References|[4]]]. Once acquiring nutrients, C. cicadae generates ATP through aerobic respiration and fermentation pathways, although aerobic respiration is preferred. For regulating aerobic respiration, C. cicadae possesses an AMPK/SIRT-1 pathway, a key component in regulating mitochondrial metabolism and ATP-generating pathways. Additionally, the fungus uses glycolysis and the TCA cycle to produce NADPH. C. cicadae can also utilize the pentose phosphate pathway to produce NADPH [6]. Additionally, the JCH-a1 polysaccharide is produced via UDP-glucose pathways, glycosyltransferase enzymes, and mannose-6-phosphate metabolism [7]. C. cicaedae also produces a plethora of secondary metabolites such as nucleosides, cyclodepsipeptides, ergosterol derivatives, and polyketide antioxidants. Nucleosides serve as intracellular metabolic intermediates to secrete bioactive compounds to form the ascocarp [3]. Nucleosides and ergosterol derivatives are known secondary metabolites in C. Cicadae only produced in certain microenvironments, with a suggested positive relationship between bacterial presence and secondary metabolite production [4]. Ergosterol derivatives assist in resisting oxidative stress through stabilizing the cellular membrane [5]. Cyclodepsipeptides produce chemicals that aid in the killing and parasitization of the host’s body [8]. Polyketide antioxidants that aid in redox regulation, stress resistance, and cellular protection [4]. Many of these secondary metabolites are used in human-medicinal applications for kidney injury, inflammation, anticancer drugs, antimicrobial drugs, and mitigating oxidative stress [3][5][8][4].
Ecology
Cordyceps cicadae thrives in moist, subtropical ecosystems with rich organic soils, where the host cicadas burrow and emerge. Globally, C. cicadae can be found throughout East Asia, including Japan and Korea, but especially in southern, central, and eastern China, where approximately 22.3% of the land area currently provides suitable habitat for C. cicadae and its host cicadas [1]. These areas have high annual precipitation, high precipitation in their driest month, and less extreme seasonality changes [8]. The most favorable environmental conditions for C. cicadae growth include high humidity, an optimal temperature of 20-25 °C, and a soil pH of 5.5-7. These specific conditions are crucial as they are the same conditions favored by the cicada nymphs, the host of C.cicadae. A shift from these conditions results in a decline of the host species, threatening the survival of C. cicadae [8]. Due to climate change, the percentage of land with these characteristics is projected to decrease in China, resulting in less overlap between the nymph habitats and those of C. cicadae. Both internal and external surfaces of C. cicadae-infected cicada nymphs host diverse bacterial and fungal communities, suggesting that microbial interactions may play a role in fungal development [8]. In research conditions, different cultivation environments have been shown to significantly alter the fungal yield, bacterial composition, and metabolite profiles, confirming the parasite’s reliance on these optimal conditions. For example, cultivation in soil richer in organic carbon and with stable moisture supports higher fungal biomass and yield, while drier or nutrient-poor soils limit growth and reduce fungal production [10]. A soil pH of 5.5-7 is favored by the bacteria associated with C. cicadae, such as Proteobacteria and Actinobacteria, directly affecting the composition and diversity of their communities, which in turn affects fungal metabolism: shifts in bacterial populations directly correlate with changes in production levels of key bioactive metabolites, including nucleosides like cordycepin and N6-(2-hydroxyethyl)adenosine (HEA), suggesting that microbial interactions may play a role in fungal development [3]. Suboptimal conditions can reduce yield or shift metabolism toward stress-resistance compounds [3].
Pathology
Cordyceps cicadae is a highly specialized entomopathogenic parasitic fungus in insects. C. cicadae primarily infects Macrosemia pieli and Platypleura kaempferi species of cicada nymphs. It is not known to infect or cause disease in humans, animals, or plants [10]. The fungus infects its host by adhering to the insect cuticle, penetrating it using a range of hydrolytic enzymes, including specific proteases such as subtilisin-like serine proteases (e.g., Pr1-type proteases) and metalloproteases, along with chitinases to degrade chitin; the major component of the cicada cuticle [4][2]. Once inside, C.cicadae proliferates within the host's internal tissues, producing secondary metabolites such as cordycepin (3’-deoxyadenosine), which has antimicrobial and immunomodulatory effects that may help suppress the host's immune response, which may help the fungus evade immune clearance [4]. C.cicadae also produces the antioxidant CP70, which protects the host cell from oxidative stress by neutralizing reactive oxygen species (ROS) and activating its cellular defense pathways against oxidative stress and inflammation (Deng et al., 2020). Over time, C. cicadae consume the nymph from the inside out, leading to the host's death. The characteristic “cicada flower” then emerges from the cicada’s remains, mummifying its nymph host and releasing spores into the environment to continue the fungal life cycle.
Current Research
C. cicadae has been valued in traditional Chinese medicine for its potential health benefits for decades. For example, ergosterol peroxide, a sterol derived from C. cicadae, suppresses the activation of kidney fibroblasts in rats, suggesting potential for anti-fibrotic therapy [5]. More recent studies indicate that a polysaccharide derived from C. cicadae mycelium, known as CH-P, can reduce hyperglycemia, oxidative stress, and inflammation in diabetic mice by modulating gut microbiota and metabolic pathways [5]. Crude polysaccharides from C. cicadae were also reported to lower blood lipid levels and enhance insulin sensitivity in diabetic rodent models. In renal studies, C. cicadae polysaccharides protected against drug-induced kidney damage by inhibiting apoptosis in renal tubular cells, indicating potential nephroprotective applications [6]. Furthermore, mycelial extracts of C. cicadae have been shown to ameliorate cisplatin-induced kidney injury in mice by modulating inflammatory and antioxidant pathways, such as the TLR4/NF-κB/MAPK and HO-1/Nrf2 pathways [8]. These effects are comparable to those observed in other medicinal fungi such as Cordyceps militaris and Ganoderma lucidum, which similarly reduce oxidative stress and inflammation, suggesting that C. cicadae shares conserved protective mechanisms with these fungi. Also, aqueous extracts of C. cicadae can create hyaluronan synthesis in human fibroblasts, pointing to possible anti-aging and dermatological benefits. In immunological research, purified polysaccharides from C. cicadae spores were shown to protect mice from oxidative stress and immune suppression, supporting their immune-enhancing activity [4].
Structural chemistry advances have identified a novel galactoglucomannan polysaccharide, JCH-a1, from C. cicadae, which demonstrated antioxidant activity and lifespan-extending effects in Caenorhabditis elegans. Research further revealed that adding nitrogen sources altered the metabolite profile of C. cicadae by enhancing ergosterol biosynthesis and secondary metabolite production, suggesting its usefulness in bioengineering. Safety studies found no harmful effects in animals given C. cicadae mycelial extracts [1]. Most recently, C. cicadae extracts were shown to alleviate aging-related cellular damage in mouse tissues via activation of the AMPK/SIRT1 pathway [10]. This research indicates growing scientific interest in C. cicadae’s clinical potential across metabolic, immune, renal, and aging systems.
References
[1] Chen, J., & He, D. (2025). Potential geographical distribution of Cordyceps cicadae and its two hosts in China under climate change. Frontiers in Microbiology, 15.
[2] Huang, A., Wu, T., Wu, X., Zhang, B., Shen, Y., Wang, S., Song, W., & Ruan, H. (2021). Analysis of Internal and External Microorganism Community of Wild Cicada Flowers and Identification of the Predominant Cordyceps cicadae Fungus. Frontiers in Microbiology, 12.
[3] Qu, Q. S., Yang, F., Zhao, C. Y., & Shi, X. Y. (2019). Analysis of the bacteria community in wild Cordyceps cicadae and its influence on the production of HEA and nucleosides in Cordyceps cicadae. Journal of Applied Microbiology, 127(6), 1759–1767.
[4] Liu, Y., Li, X., Meng, Y., Wu, Y., Jin, Y., Ma, X., Zhou, W., Tan, Y., Lin, F.-C., & Wang, H. (2025). The whole genome sequence of Cordyceps cicadae — an edible and potential medicinal fungus. Molecular Genetics and Genomics, 300(1).
[5] Tang, Z., Lin, W., Chen, Y., Feng, S., Qin, Y., Xiao, Y., Chen, H., Liu, Y., Chen, H., Bu, T., Li, Q., Cai, Y., Yao, H., & Ding, C. (2022). Extraction, Purification, Physicochemical Properties, and Activity of a New Polysaccharide From Cordyceps cicadae. Frontiers in Nutrition, 9.
[6] Zhu, R., Rong, Z., Deng, Y. “Ergosterol Peroxide from Cordyceps Cicadae Ameliorates TGF-β1-Induced Activation of Kidney Fibroblasts.” Phytomedicine, vol. 21, no. 3, Feb. 2014, pp. 372–378
[7] C.-C., Lee, L.-Y., Li, P.-Y., Huang, W.-C., Liao, J.-C., Chen, H.-Y., Huang, S.-S., & Huang, G.-J. (2020). cordyceps cicadae mycelia ameliorate cisplatin-induced acute kidney injury by suppressing the TLR4/nf-κB/MAPK and activating the HO-1/Nrf2 and SIRT-1/AMPK pathways in mice. Oxidative Medicine and Cellular Longevity, 2020, 1–17.
[8] Wang, J., Zhang, D.-M., Jia, J.-F., Peng, Q.-L., Tian, H.-Y., Wang, L., & Ye, W.-C. (2014b). Cyclodepsipeptides from the ascocarps and insect-body portions of the fungus Cordyceps cicadae. Fitoterapia, 97, 23–27.
[9] Weng, S.-C., Chou, C.-J., Lin, L.-C., Tsai, W.-J., & Kuo, Y.-C. (2002). Immunomodulatory functions of extracts from the Chinese medicinal fungus Cordyceps cicadae. Journal of Ethnopharmacology, 83(1-2), 79–85.
[10] Zeng, Z., Mou, D., Luo, L., Zhong, W., Duan, L., & Zou, X. (2021a). Different Cultivation Environments Affect the Yield, Bacterial Community and Metabolites of Cordyceps cicadae. Frontiers in Microbiology, 12.
[11] Zhu, Y., Yu, X., Ge, Q., Li, J., Wang, D., Wei, Y., & Ouyang, Z. (2020). Antioxidant and anti-aging activities of polysaccharides from Cordyceps cicadae. International Journal of Biological Macromolecules, 157, 394–400.
Edited by Ian VanDerhoef, Dalya Hocine, Lily Brumbaugh, Elfreda Raven, and Shlok Chitalia students of Jennifer Bhatnagar for BI311 General Microbiology, 2024, Boston University.
