Pseudogymnoascus destructans (white-nose syndrome fungus)

Pseudogymnoascus destructans is a psychrophilic (cold-loving) fungus that causes white-nose syndrome (WNS), an emerging disease of North American bats that has caused unprecedented population declines. The fungus is believed to have been introduced to North America from Europe or Asia (where it is present but does not cause significant mortality), but the full extent of its native range is unknown. The route of introduction is also unknown. In North America, hibernating bats become infected with P. destructans when body temperature decreases during winter torpor into the range permissive for growth of this fungus. Infected bats may develop visible fungal growth on the nose or wings, awaken more frequently from torpor, and experience a cascade of physiologic changes that result in weight loss, dehydration, electrolyte imbalances, and death. P. destructans persists in the environments of underground bat hibernation sites (hibernacula) and is believed to spread primarily by natural movements of infected bats. The first evidence of WNS in North America is from a photograph of a hibernating bat taken during winter of 2005-2006 in a hibernaculum near Albany, New York. P. destructans subsequently spread rapidly from the northeastern United States throughout much of the eastern portions of the United States and Canada, and most recently (as of May 2017) was detected in Washington State. It has killed millions of bats, threatening some species with regional extirpation and putting at risk the valuable environmental services that bats provide by eating harmful insects.

A fungus with curved conidia was isolated from the skin of little brown bats (Myotis lucifugus) and northern long-eared bats (Myotis septentrionalis) that were demonstrating signs of an unknown disease designated “white-nose syndrome”, with white growth observed on the nose and wings of affected bats (Blehert et al., 2009; Gargas et al., 2009). The newly discovered fungal pathogen was first placed in the genus Geomyces, based on initial rRNA gene sequence analysis, with the specific name destructans, but this fungus’s asymmetrically curved conidia were morphologically unlike those of congeners (Gargas et al., 2009). Based upon subsequent multi-locus sequence analysis, the fungus was reclassified to the genus Pseudogymnoascus in the family Pseudeurotiaceae (Minnis and Lindner, 2013).

The type specimen of Pseudogymnoascus destructans was isolated from the wing of a little brown bat (Myotis lucifugus) during February 2008 (Holotype BP187895; ex-type culture NHWC 20631-21) (Gargas et al., 2009). This fungus is psychrophilic and grows slowly on cornmeal agar or Sabouraud dextrose agar incubated at cold temperatures (approximately 5 to 15°C). Growth at 7°C on cornmeal agar produces a 1.0 mm diameter colony after 16 days (Gargas et al., 2009). Colonies are white marginally, with grey to grey-green, powdery centres; the reverse side is either uncoloured (cornmeal agar) or brown (Sabouraud dextrose agar) (Gargas et al., 2009; Chaturvedi et al., 2010). Optimal temperature for maximum growth rate varies among isolates but ranges from 12.5°C to 15.8°C (Verant et al., 2012), which is warmer than the typical body temperature of hibernating bats (approximately 7.2°C) (Brack, 2007). The fungus does not grow above 20°C (Verant et al., 2012).

Microscopically, P. destructans has characteristic moderately thick-walled, curved conidia and erect, hyaline, smooth, narrow and thin-walled conidiophores (Gargas et al., 2009; Chaturvedi et al., 2010). Atypical morphology is observed when cultures are incubated at temperatures greater than 12°C (Gargas et al., 2009; Verant et al., 2012). At elevated temperatures (above 15°C) hyphae become deformed and thickened and show signs of degeneration (Verant et al., 2012).

In vitro studies have demonstrated that P. destructans has diverse metabolic capacities that would support survival as a saprobe outside a host, and also produces a variety of enzymes that may serve as virulence factors (Raudabaugh and Miller, 2013). It may be similar to other environmentally-persistent fungal pathogens, such as Cryptococcus neoformans, in having a number of “dual use” enzymes, including proteinase, urease, lipase, haemolysin, chitinase, cellulase, and superoxide dismutase, that are potentially valuable for saprotrophic growth and also may serve pathogenic functions when infecting a host (Smyth et al., 2013; Reynolds and Barton, 2014). Virulence factors identified in P. destructans that may specifically contribute to skin invasion include secretion of siderophores (Mascuch et al., 2015), over-production of riboflavin (vitamin B₂) (Flieger et al., 2016), and excretion of a subtilisin-like serine protease that degrades collagen (Pannkuk et al., 2015; O'Donoghue et al., 2015).

The complete genome of P. destructans was recently published (Drees et al., 2016), which should facilitate additional exploration of unique virulence genes that contribute to skin invasion and pathogenesis in bat hosts.

Isolates of P. destructans from North America are clonal (Rajkumar et al., 2011; Ren et al., 2012; Khankhet et al., 2014), while those from Europe are more genetically diverse (Leopardi et al., 2015).

Pseudogymnoascus destructans has been detected on bats or in environments utilized by bats for hibernation in North America (United States and Canada), at least 18 European countries, and China. The native range of the fungus is unknown but is minimally presumed to include parts of Europe, where there is evidence of genetic diversification (Leopardi et al., 2015). The route of introduction to North America has not been determined. The disease has now been reported from 5 provinces in eastern Canada and 31 US states, mostly in the centre and east of the country; the fungus, but no clinical disease, has been found in an additional 2 states. An interactive map of the spread and distribution of WNS in North America is available at: https://www.sciencebase.gov/gisviewer/wns/; the latest map of distribution, along with earlier versions, can be seen at https://www.whitenosesyndrome.org/resources/map.

Pseudogymnoascus destructans is hypothesized to have been introduced to North America from Europe or Asia (Frick et al., 2010; Wibbelt et al., 2010; Warnecke et al., 2012; Minnis and Lindner, 2013; Leopardi et al., 2015, Hoyt et al. 2016). The route of introduction is unknown. Subsequent spread in North America is believed to be driven primarily by the natural movement of bats among geographically restricted patches of hibernation habitat, with climate variables restricting pathogen range (Maher et al., 2012; Wilder et al., 2015). Isolates of P. destructans from North America are clonal (Rajkumar et al., 2011; Ren et al., 2012; Khankhet et al., 2014), while those from Europe are more genetically diverse (Leopardi et al., 2015).

Bats demonstrating signs of white-nose syndrome (WNS) were first described in the field setting near Albany, New York, during the winter of 2006-2007. Biologists reported increased mortality and abnormal white growth on the nose or wings of bats (Blehert et al., 2009; Blehert, 2012). The condition was attributed to infection with an uncharacterized fungal pathogen that was subsequently identified as P. destructans (Gargas et al., 2009).Pseudogymnoascus destructans was formally demonstrated to be the causative agent of WNS in captive experiments (Lorch et al., 2011).

Since initial detection, WNS has spread rapidly throughout much of the eastern United States and eastern Canada. As of January 2017, detection of P. destructans associated with clinical signs of WNS in bat populations had been confirmed from five Canadian provinces and 31 states in the United States, including an isolated detection on the west coast in Washington State (Lorch et al., 2016). P. destructans has also been detected on bats without documented manifestation of WNS in two additional states. An interactive map of the spread and distribution of WNS in North America is available at: https://www.sciencebase.gov/gisviewer/wns/; the latest map of distribution, along with earlier versions, can be seen at https://www.whitenosesyndrome.org/resources/map.

The route by which Pseudogymnoascus destructans arrived in the United States is unknown, which limits accurate assessment of risks for additional global introduction events.

Spread of P. destructans to unaffected bat populations in the western United States, western Canada, or Central and South America by continued natural diffusion or by human-mediated processes remains a concern (Maher et al., 2012; Knudsen et al., 2013; Escobar et al., 2014; Frick et al., 2015; O'Regan et al., 2015). While it has been proposed that decreased bat community connectivity in western North America could slow pathogen spread in this region (Wilder et al., 2015), detection of P. destructans on the Pacific Coast of the United States has heightened concerns about the potential for more rapid dissemination in western regions. The route by which P. destructans was transmitted to Washington is also unknown, but the isolate genetically matches those found in eastern North America, suggesting a within-country translocation event (Lorch et al., 2016).

Clonality of North American fungal isolates has hampered capacity to document patterns of spread through genetic analysis of the pathogen. Recent work on the genetics of viruses that infect this fungus may offer a novel alternative for understanding eco-epidemiology of white-nose syndrome across North American landscapes (Thapa et al., 2016).

Millions of North American bats have died from white-nose syndrome (WNS), resulting in dramatic regional bat population declines (Frick et al., 2010; Frick et al., 2015; Reynolds et al., 2016). Insectivorous bats provide valuable pest control services. For example, bats eat insects that damage crops and forests, and that carry diseases. In the USA alone, insectivorous bats are estimated to save farmers over $3 billion annually in pest suppression services (Boyles et al., 2011). Recent experiments indicate that bat suppression of insect pests in corn (maize) fields could scale globally to one billion dollars in savings per year for that crop alone (Maine and Boyles, 2015). Many bat species in tropical and subtropical regions are also important pollinators and dispersers of seeds (Boyles et al., 2011; Kunz et al., 2011). Mortality due to WNS and other population stressors is expected to reduce the levels at which bat populations provide these valuable and irreplaceable ecosystem services.

White-nose syndrome affects all life stages of hibernating bats, and mortality at newly-affected hibernacula can be very high, resulting in substantial and rapid decreases in bat abundance (Frick et al., 2010). Millions of North American bats have died from WNS, and population declines for heavily impacted species could result in regional extirpation of some previously common species such as the little brown bat (Myotis lucifugus) and northern long-eared bat (M. septentrionalis) (Frick et al., 2010; Frick et al., 2015; Reynolds et al., 2016; Brooks, 2011; Thogmartin et al., 2013; Erickson et al., 2016).

Bat populations affected by WNS are expected to be slow to recover due to low annual fecundity, and some populations may struggle to achieve the numbers seen prior to emergence of this disease (Russell et al., 2015). Cumulative effects of other population stressors, such as mortality from wind-turbine collisions, could exacerbate disease impacts (Erickson et al., 2016). Long-term monitoring of bat populations will be vital for understanding recovery trajectories and guiding evidence-based management decisions (Russell et al., 2015).

Additionally, shifts in bat community composition and abundance have been documented in areas of the United States and Canada that have been affected by WNS (Francl et al., 2012; Frick et al., 2015). Although the implications of these declines and populations shifts are not fully understood, they are likely to exert ecological impacts (Brooks, 2011; Frick et al., 2015).

Large-scale impacts of WNS are confined to North America. Isolates of P. destructans from both North America and Europe have similar virulence in the North American little brown bat (Myotis lucifugus) (Warnecke et al., 2012). However, while skin infection with P. destructans has been detected in a number of European bat species, mass mortality attributable to infection has not been observed (Wibbelt et al., 2010; Puechmaille et al., 2011a; Puechmaille et al., 2011b; Pikula et al., 2012; Zukal et al., 2014).

Some bat species, such as the northern long-eared bat (M. septentrionalis), may consume large quantities of mosquitoes (Reiskind and Wund, 2009), and can therefore potentially benefit human health by reducing risks for transmission of vector-borne disease. Large-scale mortality due to WNS is expected to reduce these benefits.

Emergence of fungal pathogens that pose dramatic threats to stability and viability of wildlife populations or species is a relatively new phenomenon (Blehert, 2012; Fisher et al., 2012). Response to emerging fungal diseases of wildlife presents unique challenges due to limited understanding of both fungal pathogens and wildlife hosts. Fungal species, in general, are poorly studied compared to other taxa of pathogens. Few effective antifungal medications exist and those in use often have substantial side effects. Furthermore, strategies for successful development of anti-fungal vaccines are in their infancy (Blehert, 2012; Fisher et al., 2012). Similarly, insufficient knowledge about the physiology, immunology, and ecology of the multiple species of bats susceptible to white-nose syndrome (WNS) has presented challenges to outbreak management (Foley et al., 2011). Although response to the emergence of WNS was rapid by historical standards for an emergent disease of wildlife, development of effective control and prevention strategies is still in progress (Cryan et al., 2010, 2013b; Voyles et al., 2015).

Despite the severity of its impacts, WNS has fostered substantial new interest in understanding bat ecology and wildlife disease. Most appreciably, efforts to address this devastating disease have considerably advanced formalization of partnerships and response planning that will be required to combat future instances of emerging infectious diseases affecting wildlife (Foley et al., 2011; Langwig et al., 2015b; Voyles et al., 2015).