Cordyceps militaris

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Classification and Genome

Phylogeny

Kingdom 
Fungi
Phylum 
Ascomycota
Sub-phylum 
Pezizomycotina
Class 
Sordariomycetes
Sub-class 
Hypocreomycetidae
Order 
Hypocreales
Family 
Cordycipitaceae
Genus 
Cordyceps
Species 
C. militaris

Until recently, it was part of the family Clavicipitaceae, but genetic analyses of several loci split this family in three—Cordycipitaceae, Clavicipitaceae, and Ophiocordycipitaceae. Cordycipitaceae are characterized especially by their brightly colored, fleshy stromata[14].

Genome

The C. militaris genome was shotgun sequenced [18], and analysis showed a reduction in protein families (suggesting a more restricted ecology), large secretomes, and an absence of genes coding for known human mycotoxins.

Description and Distribution

Like most other Cordyceps species, C. militaris is an entomopathogen. It primarily infects the pupae stages[10]—in the ground—of various Lepidopteran species, multiplying in the host over winter. The overgrowth of hyphae eventually kill the insect, after which club-like stromata erupt from the body and through the soil. The sexual perithecial stroma is generally bright yellow or orange[9].

C. militaris is found throughout the Northern Hemisphere, with reports originating from Ireland[10] to India[5]. It has been used for centuries in traditional Chinese medicine[13], though the endemic Ophiocordyceps sinensis (formerly Cordyceps sinensis) is more widely known.

In contrast to the host specificity demonstrated by other Hypocreales parasites, C. militaris can infect various species around its widespread distribution; it has even been demonstrated to grow on germinated soybeans[18] and rice grains[4]. This generalist approach may be a consequence of the reduction in protein families involved in nutrient scavenging, evasion of host defenses, and other pathogenic genes relative to other ascomycetes[18].

Ecology

Infection

Though not as extensively studied as O. sinensis, the mechanism of infection for C. militaris is thought to be similar to others across the Hypocreales order of endoparasites[2]. A spore(s) will stick to the exoskeleton of the host—generally a larva pupating underground—forming a short germ tube with an appressorium. An infection peg formed on the ventral side of the appressorium penetrates the host’s exoskeleton using both mechanical pressed and lipases and/or proteases. Once inside, the hyphae of C. militaris will proliferate into an endosclerotium, appearing as a solid white mass of mycelium in one autopsy of an infected host[5]. This proliferation of the mycelium kills the host as the biomass replaces the host’s organs. From the overwintering endosclerotium, stromata erupt from host and protrude from the ground, usually late summer or fall[8].

Life Cycle

The protruding stromata are usually bumpy from the protrusions of the perithecial ostioles, with the spores contained in the asci within[5].

Several studies have shown C. militaris to be sexually heterothallic. However, one study[18] found it can also fruit without a opposite mating-type partner, forming a fruiting body lacking perithecia and ascospores (both MAT1-1 single mating-type, and MAT1-1/MAT1-2 hybrid)

Medicinal Properties

Current research is working to substantiate claims by traditional Chinese medicine regarding C. militaris’ efficacy in a myriad of health issues, from reversing senility to treating cancer[13]. Many of these benefits involve cordycepin, one of the first compounds characterized from the Cordyceps species and shown to have antibacterial properties[3]. Numerous reports have shown C. militaris acting on different pathways to reduce tumor growth, namely by inducing apoptosis[17] in cancerous cells and inhibiting angiogenesis[16] and metastasis[16]. Preliminary studies have shown it to be especially efficacious for leukemia[7] and non-small cell lung cancer[17] treatments. Other studies indicate its potential for treating diabetes[1], obesity[6], African trypanosomiasis[12], and for immunomodulation[15] [11].

Other names

Cordyceps militaris is also known as Scarlet Caterpillar Club, Caterpillar Killer. Its anamorph stage is Lecanicillium

References

(1)Choi SB, Park CH, Choi MK, Jun DW, Park S. Improvement of Insulin Resistance and Insulin Secretion by Water Extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% Pancreatectomized Rats. Bioscience, Biotechnology, and Biochemistry. 2004;68(11):2257-2264.

(2)Cordyceps.us (OSU). Biology: Hypocreales. Available from here

(3)Cunningham KG, Manson W, Spring FS, Hutchinson SA. Cordycepin, a metabolic product isolated from cultures of Cordyceps militaris. Nature. 1950;166(4231):949.

(4)Hong IP, Kang PD, Kim KY, Nam SH, Lee MY, Choi YS, Kim NS, Kim HK, Lee KG, Humber R. Fruit Body Formation on a Silkworm by Cordyceps militaris. Mycobiology. 2010;38(2):128-132.

(5)Kamble VR, Agre DG. Reinvestigation of insect parasite fungus Cordyceps militaris from Maharashtra. Bionano Frontier. 2012;5(2):224-225.

(6)Kim SB, Ahn B, Kim M, Ji HJ, Shin SK, Hong IP, Kim CY, Hwang BY, Lee MK. Effect of Cordyceps militaris extract and active constituents on metabolic parameters of obesity induced by high-fat diet in C58BL/6J mice. Journal of Ethnopharmacology [Internet]. 2013 Nov 11 [cited 2013 Dec 9]:1-7. Available from here

(7)Ko BS, Lu YJ, Yao WL, Liu TA, Tzean SS, Shen TL, Liou JY. Cordycepin Regulates GSK-3β/β-Catenin Signaling in Human Leukemia Cells. PLoS ONE. 2013;8(9):1-7.

(8)Mountain Lake Biological Station (UV). Scarlet Caterpillar Club, Cordyceps militaris; c2011. Available from here

(9)NCBI. Genome: Cordyceps militaris; c2011. Available from here

(10)Northern Ireland Fungus Group. Fungal Focus: The Caterpillar Killer – Cordyceps militaris. Available from here

(11)Rao YK, Fang SH, Wu WS, Tzeng YM. Constituents isolated from Cordyceps militaris suppress enhanced inflammatory mediator’s production and human cancer cell proliferation. Journal of Ethnopharmacology. 2010;131(2):281-292.

(12)Rottenberg ME, Masocha W, Ferella M, Petitto-Assis F, Goto H, Kristensson K, McCaffrey R, Wigzell H. Treatment of African trypanosomiasis with cordycepin and adenosine deaminase inhibitors in a mouse model. Journal of Infectious Diseases. 2005;192(9):1658-1665.

(13)Russell R, Paterson M. Cordyceps – A traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry. 2008;69:1469-1495.

(14)Sung GH, Hywel-Jones NL, Sung JM, Luangsard JJ, Shrestha B, Spatafora JW. Phylogenetic classification of Cordyceps and the clavicipitaceous fungi. Studies in Mycology. 2007;57:5-59.

(15)Xiong Y, Zhang S, Xu L, Song B, Huang G, Lu J, Guan S. Suppression of T-cell activation in vitro and in vivo by cordycepin from Cordyceps militaris. Journal of Surgical Research. 2013;185:912-922.

(16)Yoo HS, Shin JW, Cho JH, Son CG, Lee YW, Park SY, Cho CK. Effects of Cordyceps militaris extract on angiogenesis and tumor growth. Acta Pharmalogica Sinica. 2004;25(5):657-665.

(17)Yoon DH, Lim MH, Lee YR, Sung GH, Lee TH, Jeon BH, Cho JY, Song WO, Park H, Choi S, Kim TW. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells. Toxicology and Applied Pharmacology. 2013;273(3):659-671.

(18)Zheng P, Xia Y, Xiao G, Xiong C, Hu X, Zhang S, Zheng H, Huang Y, Zhou Y, Wang S, Zhao GP, Liu X, St Leger RJ, Wang C. Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional Chinese medicine. Genome Biology. 2011;12(11):1-21.