Persist or Perish: Can Bats Threatened with Extinction Persist and Recover from White-nose Syndrome?

Synopsis

Emerging mycoses are an increasing concern in wildlife and human health. Given the historical rarity of fungal pathogens in warm-bodied vertebrates, there is a need to better understand how to manage mycoses and facilitate recovery in affected host populations. We explore challenges to host survival and mechanisms of host recovery in three bat species (Myotis lucifugus, Perimyotis subflavus, and M. septentrionalis) threatened with extinction by the mycosis, white-nose syndrome (WNS) as it continues to spread across North America. We present evidence from the literature that bats surviving WNS are exhibiting mechanisms of avoidance (by selecting microclimates within roosts) and tolerance (by increasing winter fat reserves), which may help avoid costs of immunopathology incurred by a maladaptive host resistance response. We discuss management actions for facilitating species recovery that take into consideration disease pressures (e.g., environmental reservoirs) and mechanisms underlying persistence, and suggest strategies that alleviate costs of immunopathology and target mechanisms of avoidance (protect or create refugia) and tolerance (increase body condition). We also propose strategies that target population and species-level recovery, including increasing reproductive success and reducing other stressors (e.g., wind turbine mortality). The rarity of fungal pathogens paired with the increasing frequency of emerging mycoses in warm-bodied vertebrate systems, including humans, requires a need to challenge common conventions about how diseases operate, how hosts respond, and how these systems could be managed to increase probability of recovery in host populations.

Introduction

Anthropogenic activity is placing disproportionate pressures on natural systems, with rates that outpace evolutionary timescales, at scales beyond the natural range and dispersal reach of organisms, and magnitudes of global and catastrophic proportions (Pievani 2014; Cowie et al. 2022). As a result, a growing number of species are being pushed toward extinction (i.e., sixth mass extinction; Cowie et al. 2022). Whether species can escape extinction and recover depends on the strength of perturbation and resilience of natural systems (Gladstone-Gallagher et al. 2019) and the success of human-led recovery efforts (Grace et al. 2021).

One of the hallmarks of human impact has been the spread of non-native species, including the emergence and spread of novel pathogens to new locations and naive hosts (Jones et al. 2008). The threat of emerging fungal pathogens and mycoses is an increasing concern in global health (Fisher et al. 2012). While fungal pathogens cause a small proportion of emerging diseases (Jones et al. 2008), they drive a disproportionate number of extinctions (Fisher et al. 2012). The global mass extinction event in amphibians driven by the emerging disease, chytridiomycosis (Scheele et al. 2019), provides a cautionary tale of the scale and scope of impact derived from the human-mediated spread of a novel fungal pathogen (Wake and Vredenburg 2008).

White-nose syndrome (WNS), caused by the novel fungal pathogen Pseudogymnoascus destructans (Pd), recently emerged as a disease in North American hibernating bats (Blehert et al. 2009). Similar to chytridiomycosis, WNS mortality is rapid, widespread, and severe (Frick et al. 2010; Cheng et al. 2021). Three bat species, Myotis lucifugus (little brown bat), Perimyotis subflavus (tri-colored bat), and M. septentrionalis (northern long-eared bat), have been highly impacted by WNS with declines >90% (Cheng et al. 2021). While Pd continues to spread throughout North America, disease dynamics have largely stabilized throughout the eastern portion of the USA and Canada (Frick et al. 2017). In these areas of WNS endemicity, remnant populations persist at a subset of sites and at a fraction of their former abundance (Cheng et al. 2021). Whether affected species can escape extinction and recover from WNS remains unclear.

In this perspective, we examine the potential for species recovery in three bat species most highly impacted by WNS in North America: M. lucifugus, P. subflavus, and M. septentrionalis. We define recovery as the process of recovery, as opposed to the achievement of a recovered state (Westwood et al. 2014). We identify recovery as the period following an epidemic when disease dynamics have stabilized and population trends have stabilized or are growing (Langwig et al. 2015a). We explore mechanisms underlying persistence in remnant bat populations mediated through host resistance, avoidance, and tolerance. We also examine evidence of population- and species-level recovery. We present evidence for M. lucifugus, P. subflavus, and M. septentrionalis in this order based on availability of published information and increasing WNS impact (Cheng et al. 2021). Finally, we discuss management actions that can support populations recovering from WNS. By providing this case study on WNS, we hope larger patterns of persistence mechanisms across other emerging disease systems (e.g., chytridiomycosis; Brannelly et al. 2021) can start to arise, facilitating a larger synthesis on host recovery from disease perturbations.

WNS extinction pressure

Novel fungal pathogens increase host extinction risk

Almost all cases of disease-induced extinctions are caused by novel pathogens encountering a naive host (McCallum 2012). The human-mediated movement of Pd from Eurasia to North America in the mid-2000s introduced Pd as a novel, invading pathogen to naive North American bats (Blehert et al. 2009). Pd likely originated millions of years ago in Eurasia, possibly derived from a plant pathogen that co-evolved in parallel with the evolution of hibernation in bats (Meteyer et al. 2022). Eurasian bat species don’t experience high mortality from WNS (Puechmaille et al. 2010), despite susceptibility to infection (Pikula et al. 2012) and tolerance of high Pd loads in some species (Zukal et al. 2016). In contrast, the emergence of the disease in North America has driven widespread mass mortality with severe impacts threatening extinction in three species—M. lucifugus, P. subflavus, and M. septentrionalis (Cheng et al. 2021).

Novel fungal pathogens, as opposed to viral or bacterial pathogens, present an increased risk to naive hosts (Fisher et al. 2012). Fungal pathogens are often able to infect multiple host species and persist in the environmental reservoir, significantly increasing the risk of disease-induced extinction in susceptible hosts (De Castro and Bolker 2005; Fisher et al. 2012). Similar to other fungal pathogens, Pd is a multi-host bat pathogen and can persist in hibernacula substrate for long periods of time in the absence of bats (Lorch et al. 2013; Hoyt et al. 2015). The environmental reservoir plays a pivotal role in driving pathogen transmission and WNS-induced mass mortality (Langwig et al. 2015b; Hoyt et al. 2020) (Fig. 1).

Fig. 1.

Theory of change diagram mapping WNS pressures to mechanisms of host response and facilitation of host recovery (A) WNS mortality is driven by immunopathology and disruption to hibernation energetics. WNS threatens remnant populations through persistence of Pd in hibernacula substrate (i.e., environmental reservoir). (B) Relief from WNS pressure does not occur via resistance; rather, persistence is moderated via mechanisms of tolerance and avoidance. Re-balancing disrupted hibernation energetics is mediated by avoiding Pd/WNS at colder microsite refugia and tolerating energetic costs of WNS via increased fat reserves. Individual mechanisms of host response can scale to population- and species-level recovery. (C) Management actions facilitating recovery directly focus on reducing disease pressure and supporting mechanisms of persistence.

WNS mortality is driven by immunopathology and disruption to hibernation energetics

Hibernating bats in North America may be susceptible to WNS for several reasons that are not mutually exclusive. First, fungal pathogens are exceedingly rare in endothermic vertebrates (Berbee 2001) and often result in host immune defense mechanisms that are maladaptive (Casadevall and Pirofski 2012). Second, unlike other fungal pathogens, Pd is a specialist pathogen that invades deep within the epidermal and dermal layers of bat skin, consuming lipids and causing necrosis in glands and tissues (Meteyer et al. 2022). Lastly, winter hibernation is a particularly vulnerable time for bats because they down-regulate immune function during long torpor bouts (Moore et al. 2011) and must carefully balance a limited energy budget to survive the 4–6 months of winter (Willis 2017).

During hibernation, Pd grows unchecked during long torpor bouts when immune function is suppressed (Meteyer et al. 2012; Field et al. 2018). During short euthermic arousals, bats elicit an immune response to Pd (e.g., localized inflammatory response, production of antibodies, cell-mediated response involving production of cytokines, and an inflammatory Th17 immune response) (Field et al. 2015; Johnson et al. 2015; Lilley et al. 2017; Field et al. 2018). However, these immune responses are likely maladaptive as they are not associated with reduced fungal pathogen load and cause increased energy expenditure (Moore et al. 2013; Johnson et al. 2015; Lilley et al. 2017; Field et al. 2018; Lilley et al. 2019). Over the course of winter, Pd infection spreads throughout the bat covering the muzzle, wings, and tail membranes and causing severe tissue damage and a cascade of physiological disruptions (Warnecke et al. 2013; Verant et al. 2014). At late stages of infection, bats arouse with increasing frequency until they have depleted winter fat reserves and die of starvation (Reeder et al. 2012) (Fig. 1). WNS mortality can also occur in bats emerging in spring via a dysregulated immune response (Meteyer et al. 2012).

Mechanisms of host persistence

While Pd continues to spread throughout western North America, it has established across most of the eastern USA and Canada (https://www.whitenosesyndrome.org/where-is-wns). A large proportion of WNS-impacted populations have been extirpated from winter roosts or declined to extremely small colonies (i.e., <10 bats) (Cheng et al. 2021). There is evidence that a handful of persisting M. lucifugus populations in the northeastern USA are exhibiting positive population growth (Dobony et al. 2011; Langwig et al. 2012; Maslo et al. 2015; Frank et al. 2019). These remnant M. lucifugus populations have become a focal point in understanding mechanisms of WNS survival and evolutionary rescue.

Disease occurs when suitable conditions overlap between the host, pathogen, and environment (“disease triangle”). Within the range of Pd spread in North America, there are observed locations where WNS has not manifested in susceptible host species despite the continued presence of Pd [e.g., M. lucifugus at Tippy Dam (Gmutza et al. 2024); P. subflavus in southern culverts (Ferrari 2022); M. septentrionalis along the northeastern US coastline (Hoff 2023)]. These sites presumably exist outside the disease triangle and should be distinguished from WNS remnant populations where WNS emerged, mortality occurred, and bats are now recovering due to changes in the host, pathogen, or environment. While changes related to the pathogen (e.g., pathogen attenuation; Brannelly et al. 2021) or the environment (e.g., changes in climate; Brannelly et al. 2021) that favor host survival are possible, they have not been well studied in this system. Thus, we focus on evidence for mechanisms related to host response underlying WNS persistance, including resistance (reduced pathogen load), avoidance (reduced pathogen exposure), and tolerance (reduced disease impacts) (Wilber et al. 2024) (Fig. 1). We also review the potential for population- and species-level recovery (Fig. 1).

Evidence of reduced fungal load (“resistance”) but not via immune response

Evidence of host resistance has been proposed in some remnant M. lucifugus populations based on observations of reduced Pd loads in conjunction with population growth (Langwig et al. 2017). However, if resistance is occurring, it is not operating via host immune response, which appears to contribute to mortality rather than being protective (Moore et al. 2013; Johnson et al. 2015; Lilley et al. 2017; Field et al. 2018; Lilley et al. 2019). Further research is needed to understand the mechanisms that lead to reduced fungal loads on bats during hibernation to determine whether bat hosts have evolved resistance.

Re-balancing hibernation energetics leads to persistence

Avoidance: roosting in colder microsites may serve as refugia

Winter roost microclimate plays an important role in how bats utilize energy over hibernation (Boyles et al. 2007). In general, bats with poorer body conditions roost in colder microsites that facilitate longer torpor bouts and energy savings (Boyles et al. 2007). Temperature and humidity also play a critical role in Pd growth (Verant et al. 2012), and are important drivers in within-species pathogen burden and WNS impact (Langwig et al. 2012, 2016).

There is increasing evidence that some bats are altering hibernation behavior and physiology that may contribute to reduced pathogen exposure and burden (Lilley et al. 2016; Frank et al. 2019) (Fig. 1). At some remnant sites, bats persisting with WNS are roosting in colder microsites during hibernation in comparison to pre- and peak-WNS microsite use (Johnson et al. 2016; Lilley et al. 2016; Hopkins et al. 2021), and are exhibiting reduced arousal frequency during hibernation akin to pre-WNS counterparts (Lilley et al. 2016; Frank et al. 2019). Bats roosting in colder microsites are associated with lower Pd loads and higher WNS survival (Langwig et al. 2012; Hopkins et al. 2021). However, a recent study also found increased survival at warmer sites and posited that WNS persistence is dependent on the range of available microclimates in combination with host-related traits favoring WNS survival (Grimaudo et al. 2022), indicating an interplay among mechanisms leading to persistence. It is also unclear how broadly this strategy is used across remanant populations.

Tolerance: increased winter fat reserves allow bats to tolerate disease impacts

There is evidence that some remnant bat populations persisting with WNS have higher fat reserves than their pre-WNS counterparts (Lacki et al. 2015; Powers et al. 2015; Cheng et al. 2019; Frank et al. 2019) (Fig. 1). Without decreasing Pd loads, bats could potentially tolerate the energetic costs of WNS by increasing winter fat reserves (Cheng et al. 2019). Studies of the genetic makeups of survivors versus non-surviving M. lucifugus also found that genes likely encoding tolerance mechanisms (e.g., fat metabolic processes) may contribute to survival (Auteri and Knowles 2020; Gignoux‐Wolfsohn et al. 2021).

Increased winter fat reserves have been documented in eastern remnant populations of M. lucifugus, P. subflavus, and M. septentrionalis (Lacki et al. 2015; Powers et al. 2015; Cheng et al. 2019; Frank et al. 2019) but how widely this strategy is used by WNS survivors is unclear. There is also likely a northern limit to the ability of bats to increase pre-hibernation fat reserves, as they may already be at their upper limit of winter fat accumulation (Hranac et al. 2021). Increased fat reserves are also not observed at all remnant sites, indicating that bats are persisting due to a variety of mechanisms (Cheng et al. 2019).

Signs of potential population and species-level recovery via evolutionary rescue

Individual-level mechanisms of resistance, tolerance, and avoidance could lead to population- and species-level recovery via natural selection of beneficial and heritable traits (Wilber et al. 2024) (Fig. 1). Evolutionary rescue is a proposed scenario where species are saved from extinction via adaptation, and can be facilitated or hindered by demographic, genetic, and extrinsic factors (Carlson et al. 2014). There is some evidence of natural selection in M. lucifugus that may indicate signs of evolutionary rescue (Maslo and Fefferman 2015; Donaldson et al. 2017; Auteri and Knowles 2020; Gignoux‐Wolfsohn et al. 2021). Genes associated with adaptive change are variable across studies, but include genes associated with innate immune function (Field et al. 2015; Gignoux‐Wolfsohn et al. 2021), changes in metabolism during winter and disease progression in the wing (Field et al. 2015; Gignoux‐Wolfsohn et al. 2021), thermoregulation and production of brown fat (Lilley et al. 2020), and regulation of arousal, regulation of fat, and vocalizations (Auteri and Knowles 2020).

In contrast to M. lucifugus, studies on evolutionary rescue for P. subflavus and M. septentrionalis are scant. Given that initial population size is potentially a critical determinant in evolutionary rescue (Carlson et al. 2014), the diminished abundance of P. subflavus or M. septentrionalis (Cheng et al. 2021) makes probability of evolutionary rescue less likely. This is particularly the case for M. septentrionalis, which has been widely extirpated across its range (Cheng et al. 2021). Even in M. lucifugus, it is unclear whether an evolutionary rescue effect is occurring, in part because generation times are long (maximum lifespan of 34 years; Brunet-Rossinni and Austad 2004), and reproductive output is low (one pup per year) (Racey and Entwistle 2000). Finally, evolutionary rescue is not the only pathway for heritable traits to lead to population recovery—epigenetic and behavioral transmission of beneficial traits could also occur (O'Dea et al. 2016), and these pathways have yet to be explored.

Facilitating recovery

Species recovery for WNS-affected species in North America is facilitated through local (US state/tribal, Canadian provincial/territorial/First Nations) and federal protections programs (US Endangered Species Act and Canadian Species At-Risk Act). Endangered species protection was granted jointly for M. lucifugus, P. subflavus, and M. septentrionalis in Canada in 2014. In the USA, M. septentrionalis was recently uplisted as an endangered species (87 FR 16,442), P. subflavus has been proposed to be listed as an endangered species (87 FR 56,381), and species review for M. lucifugus is currently underway. Ultimately, recovery for these species is dependent on how different governing entities define a recovered state (Westwood et al. 2014), resources allocated to recovery efforts (Grace et al. 2021), and implementation of management strategies. We discuss how disease pressures and mechanisms of persistence can inform management actions that facilitate species recovery from WNS. Given that bat populations are persisting with WNS due to multiple mechanisms, we stress that recovery strategies should be equally varied and emphasize site-specific knowledge on bat recovery mechanisms when possible.

Alleviate the cost of immunopathology

Strategies targeting immune function may be difficult to navigate in systems where hosts suffer from immunopathology (Christie et al. 2021) (Fig. 1). The recent development of a Pd vaccine (Rocke et al. 2019) raised such concern based on evidence of immunopathology related to a maladaptive immune response in M. lucifugus (Lilley et al. 2019). However, initial vaccine trials have demonstrated that application of an oral vaccine expressing Pd antigens in captive M. lucifugus elicits a beneficial Th1 immune response associated with higher WNS survival (Rocke et al. 2019), which differs from the maladaptive Th17 response pathway elicited from natural Pd infection (Lilley et al. 2017). This is perhaps not surprising as vaccines often elicit a different response than natural infections (Krammer 2019), but highlights the need for further understanding of immune defense in bats in response to Pd and treatments targeting immune function (e.g., immunomodulatory treatments; Christie et al. 2021). Alternatively, actions that facilitate avoidance and tolerance mechanisms (described below) rather than immune function may be useful in alleviating impacts of immunopathology.

Facilitate mechanisms of avoidance

Building on evidence that bats roosting at colder microsites are persisting with WNS, winter hibernacula could be modified to create roosting sites at a range of temperatures conducive for WNS survival (Turner et al. 2022; but see Boyles et al. 2023) (Fig. 1). Manipulated sites in Pennsylvania have increased in bat abundance across all three focal species (M. lucifugus, P. subflavus, and M. septentrionalis) following habitat manipulation that creates gradients in temperatures (Turner et al. 2022).

Several points should be considered when scaling this type of strategy. First, ideal temperatures for refugia will vary by location and what constitutes as “colder” and more favorable for WNS persistence. In Wisconsin, “colder” sites facilitating WNS persistence were ∼8°C and “warmer” unfavorable sites were ∼9°C (Hopkins et al. 2021). In contrast, in the northeastern USA, post-WNS “colder” roosting temperatures were ∼2°C versus peak-WNS “warmer” roosting temperatures at ∼8°C (Lilley et al. 2016). Identifying ideal temperatures will require local knowledge and data on what microsites facilitate higher WNS survival. Second, habitat manipulation should consider climate stability and provide a spatial gradient of available microclimates (temperature and humidity) that allow bats to select preferred conditions (Boyles et al. 2023). Third, further research is needed to understand why bats choose sites and how to attract bats to refugia and avoid warm ecological traps (Hopkins et al. 2021). Lastly, avoidance strategies may lead to rapid recovery times, but be limited in the extent of recovery (i.e., recovered population size) it is able to achieve (Wilber et al. 2024).

Facilitate mechanisms of tolerance

Supporting increased body condition builds on evidence that some bats persisting with WNS have increased winter fat reserves (Cheng et al. 2019) (Fig. 1). Body condition is also associated with increased reproductive success (Barclay et al. 2004), survival (Hranac et al. 2021), and resilience against perturbations (e.g., fire; Ancillotto et al. 2021). Evidence of rapidly declining body size in M. lucifugus over a 15-year period, potentially due to nutritional stress, suggests that bats may be suffering from a shortage of food availability (Davy et al. 2022), possibly related to global declines in insect populations (Goulson 2019). A recent pilot study found that artificially created insect prey patches attracted bat activity and increased foraging activity (Frick et al. 2023). Thus, increasing insect quality and availability through habitat enhancement of foraging areas is a strategy that could facilitate recovery of WNS-affected species. Facilitating increased body condition is a long-term strategy that will require local knowledge of insect ecology and bat foraging preferences.

Facilitate population and species-level recovery

Strategies aimed at increasing population growth rates (e.g., reproductive success) and decreasing other sources of mortality will facilitate population- and species-level recovery (Fig. 1). Heated bat boxes provided for summer roosting bats have demonstrated energy savings and hasten wound healing caused by Pd skin lesions (Wilcox and Willis 2016). Enhancing body condition near summer maternity roosts may also improve reproductive success and juvenile survival (Frick et al. 2023). In addition to WNS, other threats to M. lucifugus, P. subflavus, and M. septentrionalis include collisions with wind turbines (Arnett et al. 2008), habitat destruction or deterioration for roosting and foraging habitats (Hayes and Loeb 2007), climate change (McClure et al. 2022), and human-bat conflicts (Frick et al. 2020). Particularly where populations have been reduced to small sizes, it becomes critical to also reduce impacts from other threats (De Castro and Bolker 2005). Analytical tools, such as the BatTool (Erickson et al. 2014) may also be useful in assessing the compound effects of WNS and other human-caused events on population viability.

Treat the environmental reservoir to reduce WNS threat

Despite signs of population stabilization and growth, WNS mortality continues to occur in remnant populations, but at diminished rates (Frank et al. 2019). Where WNS continues to be a threat, the use of treatment agents to “clean” the hibernacula substrate can decrease pathogen prevalence and loads on bats (Hoyt et al. 2023; Sewall et al. 2023). Development of a non-toxic treatment agent targeted at Pd will be needed to apply this strategy beyond artificial hibernacula. Fungal treatment of vertebrate hosts has been notoriously difficult to develop given the relatively close relatedness between these groups and evolution of resistant fungal strains (Fisher et al. 2020). Treatment of the environmental reservoir may provide a promising option for managing fungal pathogens without directly impacting hosts (Fig. 1).

Conclusions

Almost two decades have passed since WNS first emerged in North America, and the three bat species most highly impacted by WNS, M. lucifugus, P. subflavus, and M. septentrionalis, have experienced rapidly severe population declines and face the threat of extinction (Cheng et al. 2021). Maladaptive immune responses contribute to WNS mortality (Lilley et al. 2019). Though some populations continue to experience WNS mortality (Frank et al. 2019), some remnant populations are recovering due to a combination of avoidance [selection for microclimate refugia (Lilley et al. 2016)] and tolerance [increased winter fat reserves (Cheng et al. 2019)] mechanisms. Mechanisms of avoidance and tolerance may be leading to population- and species-level recovery, at least in some M. lucifugus populations (Auteri and Knowles 2020). Recovery strategies should focus on facilitating host persistence via tolerance and avoidance, facilitating population- and species-level recovery, and reducing WNS threat via environmental reservoir treatment.

The increasing incidence of emerging infectious diseases that threaten hosts with extinction, such as WNS, is of imminent concern for human and wildlife health. As humans continue to alter the planet, we will also inevitably continue to displace species and change environments in ways that challenge co-evolutionary species interactions (Berbee 2001; McCallum 2012). The novelty of mycoses in vertebrate hosts may challenge conventional knowledge and approaches to how emerging diseases are managed (Branelly et al. 2021). As such, we may need to re-think assumptions on how diseases operate and ensure that management actions are incorporating new system’s knowledge. To do so requires continued research and synthesis to describe the patterns and mechanisms underlying pathogenicity as well as resiliency in natural systems.

Acknowledgement

Emily Almberg and Luz DeWit provided consultation on the content in this paper and Karin Akre provided editorial support.

Conflict of interest

We declare that we have no conflicts of interest that would raise the question of bias in the work reported or the conclusions, implications, or opinions stated.

Notes

From the symposium “The scale of resilience: mechanisms of recovery across biological systems” presented at the virtual annual meeting of the Society for Integrative and Comparative Biology, January 3-7, 2024.