Ophiocordyceps sinensis, the flagship fungus of China: terminology, life strategy and ecology

Abstract

The Chinese caterpillar fungus, Ophiocordyceps sinensis (syn. Cordyceps sinensis), is one of the most famous and perhaps the most expensive fungal species in the world. Its biology largely remains a secret, and its commercial cultivation is still a dream. Owing to its medicinal, economic, social and ecological importance, and its limited distribution mainly in China, O. sinensis is herein nominated as the national fungus of China and the fungus of the year (2012) for the journal Mycology. To clarify the confusion, a standard nomenclature is proposed and recommended in this paper for a comprehensive understanding of the terms related to Cordyceps sensu lato and O. sinensis. We also review recent research on the life cycle and distribution of this fungus, parasitism of ghost moths by the fungus, the microbial community of natural Chinese cordyceps and its insect hosts, as well as the secondary metabolites produced by the fungi isolated from natural Chinese cordyceps. By taking advantage of various expertises as well as the government support, we believe that the biological secrets of O. sinensis will be unravelled gradually, and the sustainable development and utilization of this traditional medicine will be fully achieved in the future.

Keywords:

• Ophiocordyceps sinensis
• The national fungus of China
• terminology
• cordyceps
• Chinese cordyceps
• Chinese caterpillar fungus
• life strategy
• ecology

Introduction

Ophiocordyceps sinensis (Berk.) G.H. Sung et al. (syn. Cordyceps sinensis) is one of the most famous and perhaps the most expensive fungal species in the world. O. sinensis parasitizes soil-borne larvae of ghost moths on the Tibetan Plateau (Stone 2008). The fungus–caterpillar complex resulting from fungal parasitism has a long history of use in traditional Chinese medicine (TCM) as well as in traditional Tibetan medicine for the treatment of asthma, bronchial and lung inflammation, and other diseases (Zhu et al. 1998; Chen, Lee et al. 2010). The hand-collected, naturally occurring fungus–caterpillar complex is highly valued by herbalists. Due to huge market demand, limited distribution in nature and the failure of artificial cultivation of this fungus, natural O. sinensis specimens (parasitized caterpillars with fungus fruiting bodies) have been heavily harvested, resulting in the depletion of the natural stock in recent years. O. sinensis has been listed as an endangered species in China (State Council of the People's Republic of China 1999).

In addition to being medicinally and economically important, O. sinensis is also ecologically important and considered as a flagship species for its ecosystem (Cannon 2010). Consequently, O. sinensis has become the focus of substantial recent research, and its genome is currently being sequenced (An et al. 2010). Although there are several recent review articles dealing with this fungus (Paterson 2008; Winkler 2008; Zhou et al. 2009; Guo et al. 2010; Shrestha et al. 2010), the ecology of the fungus has not been emphasized, and some terms relating to Cordyceps s.l. and O. sinensis are still confusing. In this review, we summarize what is known about the ecology of O. sinensis and suggest standardization of the terms concerning these fungi. Owing to its scientific novelty and social impact in China, we suggest that O. sinensis be selected as the national fungus of China and that it be “fungus of the year” for the journal Mycology.

Ophiocordyceps sinensis as the national fungus of China

Many countries in the world have selected national flowers, birds or trees, with which they have close cultural associations, as a pictorial or cultural icon or symbol. Several fungi in China could be nominated as the “national fungus” in view of their long history of public utilization and social impact. The lingzhi fungus (Ganoderma lucidum, in Chinese) could be an excellent candidate due to its importance in TCM and Chinese culture. However, G. lucidum is distributed worldwide and is now recognized as a species complex (Hseu et al. 1996; Postnova and Skolotneva 2010), and hence traditional lingzhi can refer to species other than G. lucidum. Other fungi that are also important in China include Tricholoma matsutake (Ito & Imai) Singer, Monascus purpureus Went, and Lentinus edodes (Berk.) Singer, but these are also distributed worldwide.

We nominate O. sinensis as the national fungus of China based on the following characteristics:

1.	O. sinensis is distributed mainly in China and is even referred to as the “Chinese caterpillar fungus”. According to recent estimates, China accounts for more than 90% of its known production areas (Winkler 2008) and more than 95% of its annual yield (Winkler 2010).
2.	O. sinensis has close cultural connections to China, and natural O. sinensis specimens have been used as a TCM or an important dietary supplement since ancient times. Its pharmacological properties were discovered 1,500 years ago by herdsmen who observed that their yaks became energized after consuming it (Hollobaugh 1993). For a long time, however, the fungus was so difficult to obtain, and expensive, that only nobles and Chinese emperors were able to use it. This fungus first gained worldwide attention when it was credited for the success of Chinese woman athletes at the National Games in Beijing in 1993 (Steinkraus and Whitfield 1994; Stone 2008). Documentation of O. sinensis in China can be traced to the middle 15th century in Tibetan literature or to the late 17th century in Chinese literature (Winkler 2008).
3.	Sales of natural O. sinensis specimens represent an important portion of the gross domestic product of local governments and represent most, if not all, of the cash income of many rural families. About 80% of families in the major production areas are involved in collection of natural O. sinensis specimens, and cash income from sales of this resource accounts for 50–80% of their total income (Ma 2010). Currently, more than 300,000 Chinese citizens in local regions rely on the collection and sale of this resource (Ma 2010). No other fungus in China, or in any other country, plays such an important role in the local economy. The price of natural O. sinensis specimens has been rising in recent years and is currently higher than that of gold owing to its limited distribution and yield.
4.	O. sinensis is considered a flagship species of the Tibetan Plateau (Cannon 2010), and over-harvesting of the fungus poses a threat to this fragile ecosystem. The Tibetan Plateau is an especially important ecosystem as it is the source of many important rivers in Asia. It is estimated that in the Nyingchi district of Tibet alone, about 100,000 m2 of grasslands are damaged each year by human activities such as digging natural O. sinensis specimens out of soil, soil compaction by people and vehicles, and destruction from shrub cuttings to establish camps or to use as fuel for campfires (Zhuo et al. 2008). These destroyed grasslands are difficult to recover and can even lead to desertification (Yang 2008).
5.	O. sinensis is a fascinating organism, and there are still many unanswered questions concerning its biology. These include “Why is its distribution so limited?”, “How has the fungus coevolved with its insect hosts and with the plant hosts of the insects?”, and “Does parasitism of ghost moths by O. sinensis reduce herbivory and thereby alter the plant community?” Recognizing O. sinensis as the national fungus of China will promote research on its biology, ecology, and conservation.

Terminology related to Cordyceps and O. sinensis

Cordyceps is a traditional genus of ascomycete (sac fungi) that includes about 400 described species (Stensrud et al. 2005). All Cordyceps species are endoparasitic, mainly parasitizing insects and other arthropods (thus referred to as entomopathogenic fungi); a few parasitize other fungi. Recent phylogenetic analysis has shown that the traditional genus Cordyceps is not monophyletic and most former species of this genus are now assigned to Cordyceps, Ophiocordyceps, Metacordyceps, and Elaphocordyceps (Sung et al. 2007). The most important of these species for TCM are O. sinensis, C. cicada, C. militaris and E. ophioglossoides. Of all Cordyceps s.l. species, the best known is O. sinensis.

The close relationship between species of Cordyceps s.l. and their hosts has resulted in confusing terminology. For example, the fungus–host entities have often been referred to by the Latin name of the fungus, and this has puzzled non-scientists and some researchers. Here, we propose a standard nomenclature (Table 1). Because the fungus–host complex is the result of parasitism of a host by a fungus, the complex should be described by a word with general meaning. Analogous to the terms pseudomonad/Pseudomonas or fungi/Fungi, we suggest that the term “cordyceps” (lowercase and without italics) should be used to refer any cordyceps fungus–host complex (i.e. in Chinese), and the term “cordyceps fungus” (i.e. in Chinese) should be used when referring only to the fungus that forms cordyceps. “Cordycipitaceous fungus” (i.e. in Chinese) should be used to represent the fungal species within the family Cordycipitaceae. “Cordyceps s.l.” would refer to any species in the genus Cordyceps s.s. and in the closely related genera Ophiocordyceps, Metacordyceps, and Elaphocordyceps that were traditionally referred to as Cordyceps (i.e. in Chinese). Two English terms, “vegetable caterpillar” and “vegetable caterpillar fungus”, are found in some publications (Buller 1894; Salmon 1951) or in Google searches, but these terms are misnomers and should not be used.

Table 1. Recommended terminology concerning Cordyceps, Ophiocordyceps sinensis, and host insects

Chinese name (pin yin)	English name	Latin name	Note
(chong cao)	cordyceps		Specimens of the cordyceps fungus–host complex occurring in nature or artificially cultivated
(chong cao jun)	cordyceps fungus (pl. cordyceps fungi)		The fungi that infect insects or other hosts and form cordyceps
(chong cao jun shu)	fungi in Cordyceps s.l.	Cordyceps s.l.	Fungi belonging to the genus Cordyceps s.l.
(dong cong xia cao)	Chinese cordyceps		The O. sinensis–ghost moth caterpillar combination used by herbalists in TCM
(dong cong xia cao jun)	Chinese caterpillar fungus (or Chinese cordyceps fungus)	Ophiocordyceps sinensis	The main fungal component of Chinese cordyceps
(tian ran dong chong xia chao)	natural Chinese cordyceps		Chinese cordyceps from nature
(dong cong xia cao ding zhi zhen jun)	Chinese cordyceps- colonizing fungus		Any fungi that colonize natural Chinese cordyceps

Ophiocordyceps sinensis and Chinese caterpillar fungus are normally represented by the terms “dong chong xia cao” ( in Chinese) or “dong chong xia cao jun” ( in Chinese) (Winkler 2008). To differentiate between these terms and in recognition of the importance of this fungus to China, we recommend that the term “Chinese cordyceps” ( or in Chinese) (Wang et al. 1996) should be used when referring to the O. sinensis–ghost moth caterpillar complex, while “Chinese cordyceps fungus” or “Chinese caterpillar fungus” ( in Chinese) should be used as the common English names for the fungus. The term “natural O. sinensis specimens” has been used in TCM, and we recommend that the term “natural Chinese cordyceps” ( in Chinese) should be used for O. sinensis–ghost moth caterpillar complexes collected in nature. The term “winter worm, summer grass” is the literal translation of the Chinese name “” and should not be used because it lacks scientific meaning. Some people use the term “aweto” to refer to “”, but aweto is the Māori name for Ophiocordyceps robertsii (syn. Cordyceps robertsii), a species from New Zealand (http://en.wikipedia.org/wiki/Ophiocordyceps_sinensis). The equivalent names for “” in other countries or regions were summarized by Shrestha et al. (2010). Researchers and others should be aware that in TCM and in a few Chinese publications, “chong cao” ( in Chinese) represented either “dong chong xia cao” ( in Chinese), i.e. Chinese cordyceps, or “chong cao” ( in Chinese), i.e. cordyceps.

Life cycle and distribution of O. sinensis

Ophiocordyceps sinensis has an unusual life cycle in nature (Figure 1). In late autumn, the fungus infects underground larvae of ghost moths within the family Hepialidae. It is not known how the fungus infects the caterpillar; perhaps the caterpillar ingests a fungal spore, perhaps a fungal hypha penetrates a spiracle of the insect, or perhaps an ascospore or a conidium adhering to the insect surface germinates and directly penetrates the insect's cuticle. After entering the caterpillar's body, the fungus grows vegetatively and fills the caterpillar with threadlike hyphae. Even infected by the fungus, the larvae can still move from positions 5(10)–25(35) cm to positions 2–5 cm beneath the soil surface before dying with the head upward. The fungus then grows out from the dead host (usually from the head) and forms a small stroma bud before soil freezing in winter (Buenz et al. 2005; Li et al. 2006). In the following spring, the stroma bud grows upward, emerging above the soil surface and forming a stalked fruiting body (a sexual, perithecial stroma) (Pu and Li 1996; Buenz et al. 2005). Thread-like ascospores are released from the perithecia and can presumably infect new caterpillars. In addition to the ascospores, O. sinensis can also produce asexual conidia. The anamorph of the fungus is widely recognized as Hirsutella sinensis (Liu et al. 1989). The conidia are produced by conidiogenous cells formed on vegetative hyphae or germinated ascospores.

Figure 1. Schematic diagram showing the life cycle of O. sinensis.

Growth and reproduction of O. sinensis in nature requires a host insect, but the fungus has a wide host range that includes more than 50 species within the family Hepialidae (Lepidoptera) (Wang and Yao 2011). Generally, the life cycle of O. sinensis insect hosts requires 2 or 3 years. The larval stages live underground and feed on roots of plants of more than 19 angiosperm families in alpine meadows on the Tibetan Plateau (Zhu et al. 2004).

Natural Chinese cordyceps are a biological community that includes, in addition to the Chinese caterpillar fungus and the insect host, many other microorganisms. Although the effect of those microorganisms on natural Chinese cordyceps is largely unknown, some other fungi can facilitate infection by the Chinese caterpillar fungus into the ghost moth larva (Li et al. 2010). In addition to biotic factors, some environment factors, such as temperature, humidity and light, may also affect the infection and sporulation of O. sinensis (Zhang, Yu, et al. 2011).

Chinese cordyceps are distributed in alpine regions of the Tibetan Plateau between 3000 and 5000 m asl or up to the snow line, depending on the locality. They are mainly found in China, including eastern Tibet, eastern Qinghai, western Sichuan, northern Yunnan, and southwestern Gansu provinces (Li et al. 2010; Yang et al. 2010). Tibet and Qinghai are the two major production regions of natural Chinese cordyceps in China, accounting for 80% of the total yields (Ma 2010). O. sinensis is also found in other Himalayan countries, including Nepal, Bhutan and India (Shrestha et al. 2010). The global distribution area of the fungus is estimated to be about 1 million km², which represents about 10% of the area of the Chinese mainland (Zhang, Li, et al. 2010). Distribution of natural Chinese cordyceps with altitude has varied over time. Compared to 30 years ago, O. sinensis now occurs at higher altitudes in its core distribution regions (Nagqu and Qamdo in Tibet and Yushu in Qinghai) but at lower altitudes in peripheral distribution regions (Yang et al. 2010). O. sinensis has not been reported from western regions of the Tibetan Plateau, perhaps due to the dry climate. The distribution of this fungus is very limited probably because it is psychrophilic and must parasitize belowground larvae of ghost moths. Chinese cordyceps reported outside of “High Asia” were erroneously identified and refer to other Cordyceps species, e.g. Cordyceps militaris, Cordyceps gunnii (Shrestha et al. 2010; Yang et al. 2010).

Although the distribution of natural Chinese cordyceps is limited and its production has decreased (Chen, Zhong et al. 2010), the annual yield of this natural resource in China has been as high as 100–200 tons in recent years (Ma 2010; Zhang, Li et al. 2010). Among the five provinces, Qinghai has the largest production (about 100 tons per year), and Yushu and Guoluo contributed 80% of the total yield of this province (Cai and Sun 2010). In Tibet, the total yield is about 40 tons, with 80% contributed by Nagqu and Qamdo (Xu et al. 2010).

Parasitism of host insects by O. sinensis and its ecological consequence

Ophiocordyceps sinensis infects insect larvae in soil. A field investigation revealed that the highest infection occurred when 4^th to 5^th instar larvae were shedding old cuticles and forming new cuticles (Yang et al. 1989). In nature, this occurs from early to mid-August and overlaps with the time when O. sinensis releases sexual ascospores (Yang et al. 1989). Larvae at less advanced stages are seldom infected probably due to their limited movement and food intake, and those at more advanced stages are seldom infected probably owing to increased resistance. When larvae are infected, they become less active in 6–10 days and die in 15–25 days; infected larvae, however, often move to positions 2–5 cm beneath the soil surface before dying, which facilitates the growth of the fruiting body and its emergence from the soil in the next year (Yang et al. 1989). A small stroma bud often grows from the head of infected larvae before the soil freezes in winter. Local people have observed larvae with small stroma buds that were alive and able to move.

O. sinensis hyphal bodies were detected in the hemocoels of 10–20% of the 3^rd to 8^th instar larvae that were collected in nature (Li et al. 1998). Artificially inoculated larvae have also been used to study the growth of O. sinensis within the body of host insect larvae (Zeng et al. 2006). Mycelia of O. sinensis enter the hemocoel of the larva and then fragment into fusiform hyphae that multiply by yeast-type budding. After plasmogamy between hyphal fragments occurs, the mycelia of O. sinensis fill the hemocoel (Zeng et al. 2006). Two cuticle-degrading serine protease genes (csp1 and csp2) from O. sinensis have been cloned and found to be involved in the degradation of host cuticle proteins (Zhang et al. 2008).

Various factors can influence the infection process. The presence of other fungi shortened the time required by O. sinensis to mummify the host larva from 50 days to 3–5 days and increased the infection rate from 3 to 60% (Li et al. 2010). Loose soil structure and precipitation facilitate the movement of O. sinensis spores into soil and thereby increase infection (Yang et al. 1989). Conditions of generally low temperatures with substantial differences between day and night temperatures can increase the vertical movements of larvae, thus increase the probability that they encounter O. sinensis spores and become infected (Yang et al. 1989).

Ghost moths can seriously damage and even kill plants in some ecosystems. For example, parasitism of ghost moths by nematodes in California, USA, greatly affected the abundance of lupine, which would be the dominant plant in the absence of ghost moths (Stock et al. 1996). In the tripartite relationship between O. sinensis, insects, and plants, there is significant dependence of higher trophic levels (the fungus is at the top, the plant is at the bottom) on lower trophic levels, and it is possible that the three components together constitute a relatively stable system. Whether overharvest of natural Chinese cordyceps could result in increased herbivory and thereby alter the plant community is largely unknown.

Microbial community of natural Chinese cordyceps and host caterpillars

In attempts to determine the anamorph of O. sinensis (which is now recognized to be Hirsutella sinensis), researchers have isolated many fungi from natural Chinese cordyceps. Jiang and Yao (2002, 2003) summarized the fungi associated with natural Chinese cordyceps during 1980s and 1990s, and their list included 22 species belonging to 13 genera (Jiang and Yao 2002, 2003). The list included seven novel species and also some taxa with nomenclatural problems. After their reviews, an additional fungus, Pseudogymnoascus roseus, was reported (Jiang and Yao 2006). Some of these fungi were found to have chemical components and/or pharmaceutical values similar to those of O. sinensis, and fermented mycelial products have been developed and applied in clinical practice (Table 2). Among these products, Bailing capsules and Jinshuibao capsules have each achieved annual sales of over RMB 100 million.

Table 2. Fungi that have been isolated from natural Chinese cordyceps and developed into health products^a

Fungus	Product	Note
Hirsutella sinensis = Cephalosporium dongchongxiacae = Hirsutella hepiali = Synnematium sinense	(Bailing capsule)	The accepted anamorph of O. sinensis; approved for production as one of the state-level new drugs in 1988 in China; Described in the Chinese pharmacopoeia since 2005.
Paecilomyces hepiali	(Jinshuibao capsule)	Approved as one of the state-level new drugs in 1987 in China; described in the Chinese pharmacopoeia since 2000.
Mortierella hepiali	(Zhiling capsule)	Approved for production in 1985; described in the Chinese pharmacopoeia since 2010.
Cephalosporium sinensis	(Ningxinbao capsule)	Approved for production in 1985.
Gliocladium roseum	(Xinganbao capsule)	Approved for production in 1987.
Paecilomyces sinensis	(Chongcaojun capsule)	Production has been prohibited since 2001.
Scydalium sp.	(Chongcao capsule)
Tolypocladium sinense	(Bo'ao chongcao oral liquid)
^aRefer to Guo et al. (2003) and Ke (2005).

To delineate the fungal community of natural Chinese cordyceps, researchers have recently combined culture-dependent and -independent approaches (Zhang YJ, Zhang S, et al. 2010). Using a culture-dependent method, the researchers detected 572 fungal strains and 92 putative operational taxonomic units (OTUs) associated with natural Chinese cordyceps. Using a culture-independent method, the researchers detected 490 fungal clones (from approximately 3000 clones of ITS fragments representing the DNA of the entire fungal community), and 118 putative fungal OTUs. Which fungal species are determined to be most abundant depends on the method (culture-dependent or -independent) and on the tissue (stromata, sclerotia, and external mycelial cortices) (Zhang, Sun et al. 2010; Zhang YJ, Zhang S, et al. 2010). Only 13 OTUs were detected simultaneously by both methods, suggesting that the fungi associated with natural Chinese cordyceps are very diverse. Many potential novel fungal lineages were also detected by each of the two methods. The effects of these fungi on the life cycle of O. sinensis in nature and their potential application in the artificial cultivation of Chinese cordyceps warrant study.

Culture-dependent and -independent methods have also been used to investigate the diversity of fungi and bacteria in intestines of naturally collected or artificially reared host larvae (Yu et al. 2008). Insect intestines harbour a diverse microbial community that can affect host nutrition, physiology, and survival. Fungi within the genera Cryptococcus, Geomyces, Trichosporon, and Mortierella were detected in the intestines of different insect hosts (Yu et al. 2008). In addition, the frequency of occurrence of bacteria, fungi, and actinomycetes differed among the intestines of wild larvae, laboratory-reared larvae, and mummified larvae (Zhang, Ma et al. 2009), and the abundance of bacterial species differed between intestines of wild and laboratory-reared larvae (Zhuo et al. 2004; Liu et al. 2008). The effect of these microorganisms on larval growth and development requires investigation.

Although most microorganisms associated with insect host larvae are not pathogens, some are like O. sinensis in that they cause host death. These other pathogens, which include many fungi, bacteria and nematodes (Zeng and Yin 2003), can interfere with the large-scale rearing of host larvae for the purpose of commercial cultivation of Chinese cordyceps. Paecilomyces spp., Metarhizium spp., and Beauveria spp. are among the fungi that can cause serious diseases in host insect populations (Zeng and Yin 2003). These diseases and their possible control methods have been described in several reports (Chen et al. 1991; Zeng and Chen 2001; Zeng 2008).

Secondary metabolites produced by fungi isolated from natural Chinese cordyceps

As noted earlier, Chinese cordyceps is the combination of O. sinensis and a dead caterpillar of a ghost moth. Researchers have suspected that the fungal component could be a valuable source of bioactive metabolites, and extracts prepared from selected species of the Chinese cordyceps-colonizing fungi have been subjected to chemical investigation. Some bioactive secondary metabolites that have been discovered are briefly described in the following paragraphs (Figure 2).

Figure 2. Structures of the bioactive secondary metabolites identified from the Chinese cordyceps-colonizing fungi.

Two new epipolythiodioxopiperazines (ETPs) (Gardiner et al. 2005), gliocladicillins A (Figure 2(1)) and B, along with the known ETPs, 11,11′-dideoxyverticillin A and 11′-deoxyverticillin A (Figure 2(2)) (Son et al. 1999), have been isolated from Gliocladium sp. The two novel compounds, gliocladicillins A and B inhibited the proliferation of HeLa, HepG2, and MCF-7 cells; further study demonstrated that they induced HeLa cell apoptosis via both extrinsic and intrinsic pathways (Chen et al. 2009). In addition, they showed profound in vivo inhibitory effects on melanoma B16 cells implanted into immunodeficient mice (Chen et al. 2009). The known ETP, 11′-deoxyverticillin A (Figure 2(2)), was found to enhance the cellular autophagic process, which requires both PARP and RIP-1 participation and which precedes and possibly augments the caspase-dependent apoptotic cell death (Zhang, Chen, et al. 2011). Two new p-terphenyl type metabolites, gliocladinins A (Figure 2(3)) and B, were also identified from the same Gliocladium sp. (Guo et al. 2007); they showed modest antimicrobial activity against Staphylococcus aureus (ATCC 6538) and cytotoxicity against HeLa and HCT116 cells.

A group of new diketopiperazines (e.g. epicoccin A; Figure 2(4)) with modest antimicrobial activity were identified from a strain of Epicoccum nigrum (Guo, Sun, Gao, Chen et al. 2009, Zhang et al. 2007). Cyclic pentapeptides (e.g. cycloaspeptide F; Figure 2(5)), N-hydroxypyridones (e.g. militarinones E; Figure 2(6)), phenylhydrazones, and farylhydrazones (Figure 2(7)) were all isolated from the crude extract of Isaria farinosa. Cycloaspeptides F (Figure 2(5)) and G showed cytotoxic effects against HeLa and MCF7 cell lines, whereas militarinone E (Figure 2(6)) showed significant cytotoxicity against A549 cells (Zhang, Liu et al. 2009; Ma et al. 2011). New trichocladinols (Figure 2(8)) were isolated from cultures of Trichocladium opacum; these compounds showed modest cytotoxic effects against the human tumour cell lines HeLa and MCF-7 (Guo, Sun, Gao, Niu et al. 2009).

These results demonstrate that Chinese cordyceps-colonizing fungi are a rich source of bioactive compounds. We suspect that these compounds function in the interaction between the fungi, the host and other microorganisms, but determining whether these compounds are produced in vivo and whether they are important in these interactions will require additional research.

Conclusion

The recognition of Ophiocordyceps sinensis as the national fungus of China and “fungus of the year” for the journal Mycology will make scientists in different disciplines more aware of O. sinensis and thereby promote new research on this interesting and important fungus. Our understanding of the biology and ecology of natural Chinese cordyceps is far from complete. For example, the coevolution between O. sinensis and host insects requires investigation. The function of microorganisms associated with natural Chinese cordyceps should be further evaluated. The effect of parasitism of ghost moths by O. sinensis on the natural plant community of the Tibetan Plateau is unknown. Finally, as an endangered species that is endemic to the Tibetan Plateau, O. sinensis requires conservation and has already attracted the attention of international public agencies such as the World Wildlife Fund (WWF) and the Centre Agriculture Bioscience International (CABI). In 2010, the International Center of Ophiocordyceps sinensis Research and Information (http://www.icosri.org/) was established and approved by the Chinese Ministry of Agriculture. We believe that collaboration among scientists, governmental and non-governmental agencies, and other stakeholders can protect O. sinensis from extinction and ensure the sustainable use of this traditional medicine and natural resource.

Acknowledgements

This study was supported by grants from the National Plans of Sciences and Technology (2007BAI32B04), the cooperative project between Guangdong Province and Chinese Academy of Sciences (2009B091300015), the National Science Foundation of China (81102759; 31140013), and the Specialized Research Fund for the Doctoral Program of Higher Education (20101401120007). The authors are grateful to Professor Yongsheng Che for his critical comments on the manuscript. We also thank Professor Bruce Jaffee (University of California at Davis) for serving as a pre-submission technical editor.