REVIEW doi:10.1038/nature10947 Emerging fungal threats to animal, plant and ecosystem health Matthew C. Fisher1, Daniel. A. Henk1, Cheryl J. Briggs2, John S. Brownstein3, Lawrence C. Madoff4, Sarah L. McCraw5 & Sarah J. Gurr5 The past two decades have seen an increasing numberof virulent infectious diseases in natural populations and managed landscapes. In both animals and plants, an unprecedented number of fungal and fungal-like diseases have recently caused some of the most severe die-offs and extinctions ever witnessed in wild species, and are jeopardizing food security. Human activity is intensifying fungal disease dispersal by modifying natural environments and thus creating new opportunities for evolution. We argue that nascent fungal infections will cause increasing attrition of biodiversity, with wider implications for human and ecosystem health, unless steps are taken to tighten biosecurity worldwide. E merging infectiousdiseases(EIDs)causedby fungiareincreasingly recognized as presenting a worldwide threat to food security1,2 (Table 1 and Supplementary Table 1). This is not a new problem and fungi have long been known to constitute a widespread threat to plant species. Plant disease epidemics caused by fungi and the fungal-like oomycetes have altered the course of human history. In the nineteenth century, late blight led to starvation, economic ruin and the downfall of the English government during the Irish potato famine and, in the twentieth century, Dutch elm blight and chestnut blight laid bare urban and forest landscapes. The threat of plant disease has not abated, in fact it is heightened by resource-rich farming practices and exaggerated in the landscape by microbial adaptation to new ecosystems, brought about by trade and transportation3, and by climate fluctuations4,5. However, pathogenic fungi (also known as mycoses) have not been widely recognized as posing major threats to animal health. This per- ception is changing rapidly owing to the recent occurrence of several high-profile declines in wildlife caused by the emergence of previously unknown fungi6,7. For example, during March 2007, a routine census of bats hibernating in New York State revealed mass mortalities8. Within a group of closely clustered caves, four species of bats were marked by a striking fungus growing on their muzzles and wing membranes, and the name ‘white nose syndrome’ (WNS) was coined. After the initial out- break, the ascomycete fungus Geomyces destructans was shown to fulfil Koch’s postulates and was described as the cause of WNS in American bat species9,10. Mortalities exhibiting WNS have subsequently been found in an increasing number of bat overwintering sites and, by 2010, the infection was confirmed to have emerged in at least 115 roosts across the United States and Canada, spanning over 1,200 km (ref. 11). Bat numbers across affected sites have declined by over 70% and ana- lyses have shown that at least one affected species, the little brown bat Myotis lucifugus, has a greater than 99% chance of becoming locally extinct within the next 16 years (ref. 11). Other species of bats across this region are declining as a consequence of this infection, and the prognosis for their survival and their role in supporting healthy ecosys- tems, is poor12. Cases of thissort arenolongerperceived tobeatypical. The probability of extinction is increasing for some species of North American bats, but another fungal infection has caused the greatest disease-driven loss of biodiversity ever documented. The skin-infecting amphibian fungus Batrachochytrium dendrobatidis was discovered in 1997 (ref. 13) and named in 1999 (ref. 14). B. dendrobatidis has been shown to infect over 500 species of amphibians in 54 countries, on all continents where amphibians are found15,16, and is highly pathogenic across a wide diversity of species. Studies using preserved amphibian specimens showed that the first appearance of B.dendrobatidis in the Americascoincided with a wave of population declines that began in southern Mexico in the 1970s and proceeded through Central America to reach the Panamanian isthmus in 2007 (ref. 17). As a consequence of the infection, some areas of central America have lost over 40% of their amphibian species18, a loss that has resulted in measurable ecosystem-level changes19. This spatiotemporal pattern has been broadly mirrored in other continents15, and ongoing reductions in amphibian diversity owing to chytridiomycosis have contributed to nearly half of all amphibian species being in decline worldwide20. Fungal infections causing widespread population declines are not limited to crops, bats and frogs studies show that they are emerging as pathogens across diverse taxa (Table 1), including soft corals (for example, sea-fan aspergillosis caused by Aspergillus sydowii)21, bees (the microsporidian fungus Nosema sp. associated with colony collapse disorder)22, and as human and wildlife pathogens in previously non- endemic regions (for example, the emergent virulent VGII lineage of Cryptococcus gattii in the northwest America23 and Cryptococcus neoformans across southeast Asia24). The oomycetes have life histories similar to those of fungi and are also emerging as aggressive pathogens of animals, causing declines in freshwater brown crayfish (for example, the crayfish plague caused by Aphanomyces astaci)25, Tilapia fish (for example, epizootic ulcerative syndrome caused by A. invadans)26 and many species of plants27,28. Although the direct causal relationship is uncertain in some of these diverse host–pathogen relationships, it seems that pathogenic fungi are having a pronounced effect on the global biota1. Increasing risk of biodiversity loss by Fungi For infectious disease systems, theory predicts that pathogens will co- evolve with, rather than extirpate, their hosts29,30. Such evolutionary dynamics mirror population-level processes in which density depend- ence leads to the loss of pathogens before their hosts are driven extinct31. For these reasons, infection has not been widely acknowledged as an 1 Department of Infectious Disease Epidemiology, Imperial College, London W2 1PG, UK. 2 Department of Ecology, Evolution and Marine Biology, University of California, Santa Barbara, California 93106- 9620, USA. 3 Department of Pediatrics, Harvard Medical School, Children’s Hospital Boston, Massachusetts 02115, USA. 4 ProMED, International Society for Infectious Diseases and Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Massachusetts 01655, USA. 5 Department of Plant Sciences, University of Oxford, Oxford OX1 3RB, UK. 1 8 6 | N A T U R E | V O L 4 8 4 | 1 2 A P R I L 2 0 1 2 Macmillan Publishers Limited. All rights reserved ©2012

Table 1 | Major fungal organisms posing threats to animal and plant species. Host Pathogen (Phylum) Disease dynamicsleading to mass mortality in animal and plant hosts Amphibian species (for example, the common midwife toad, Alytes obstetricans) Batrachochytrium dendrobatidis (Chytridiomycota) Worldwide dispersal of a hypervirulent lineage by trade64. Ultra-generalist pathogen manifesting spillover between tolerant/susceptible species. Extent of chytridiomycosis is dependent on biotic and abiotic context15,82 . Rice (Oryza sativa) Magnaporthe grisea species complex on 50 grass and sedge species, including wheat and barley Magnaporthe oryzae (Ascomycota) Rice blast disease in 85 countries, causing 10–35% loss of harvest. Global blast population structure determined by deployment of seeds with inbred race-specific disease resistance (RSR). Invasionsoccur by ‘host hops’ and altered pathogen demographics. Bat spp. (little brown bats, Myotis lucifugus) Geomyces destructans (Ascomycota) New invasion of North American bat roosts occurred in approximately 2006, and disease is spreading rapidly8. Pathogen reservoir may exist in cave soil. Disease is more aggressive compared tosimilar infections inEuropean bats, possibly owing to differences in roosts and host life histories65. Wheat (Triticum aestivum) 28 Puccinia graminis f. tritici species, but P. graminis is found on 365 cereal or grass species Puccinia graminis (Basidiomycota) Wheat stem rust is present on six continents. Population structure is determined by deployment of RSR cultivars and long-distance spread of aeciospores. Strain Ug99 poses a notable threat to resistant wheat varieties, causing up to 100% crop loss. Coral species (for example, the sea fan, Gorgonia ventalina) Aspergillus sydowii (Ascomycota) Sea-fan aspergillosis caused by a common terrestrial soil fungus21,86. Epizootics are associated with warm- temperature anomalies. Coral immunosuppression is probably a factor causing decline. Bee species (for example, the hive of the domestic honeybee (Apis mellifera) suffering colony collapse disorder) Nosema species (Microsporidia) Microsporidian fungal infections are associated with colony collapse disorder and declining populations. Pathogen prevalence is probably a part of a multifactorial phenomenon that includes environmental stressors and polyparasitism87,88. Sea turtle species (the loggerhead turtle, Caretta caretta) Fusarium solani (Ascomycota) Soil-dwelling saprotroph and phytopathogenic fungus. Infection causeshatchfailure in loggerhead turtle nests and suboptimal juveniles44. The disease dynamics fulfil Koch’s postulates. Environmental forcing is suspected but not proven. Images in Table 1, with permission: A. obstetricans chytridiomycosis mortalities, M.C.F. M. oryzae, N. Talbot WNS-affected little brown bats, A. Hicks P. graminis, R. Mago G. ventalina infected with A. sydowii, D. Harvell A. mellifera hive suffering from colony collapse disorder, J. Evans sea turtle eggs infected with F. solani, J. Dieguez-Uribeondo ´ and A. Marco. REVIEW RESEARCH 1 2 A P R I L 2 0 1 2 | V O L 4 8 4 | N A T U R E | 1 8 7 Macmillan Publishers Limited. All rights reserved ©2012