Cutaneous fungal pathogens other than G. destructans
that infect invertebrates interfere with water balance of the host. Laboratory experiments reveal that fungal infections cause death by dehydration in dog ticks (Dermacentor variabilis
), even at higher levels of humidity (greater than 90% relative humidity at 25°C) than are typically sustained under natural conditions [29
]. In certain insects, symbiotic fungi in the glands of normal cuticle help maintain homeostasis and prevent infection by pathogenic conidial fungi; without these symbionts, pathogenic fungi colonize the cuticle and subsequently cause death by dehydration [29
Although G. destructans
infection is limited to skin, its severe invasion and replacement of skin structures is not characteristic of typical dermatophytes such as Microsporum gypseum
, Trichophyton rubrum
and Geomyces pannorum
. Dermatophytes of mammals typically colonize the superficial epidermis, hair and nails and do not invade living tissue [47
]. The ability of G. destructans
to invade the wing skin of hibernating bats is unlike that of any known cutaneous fungal pathogens in terrestrial mammals. As discussed in this article, we propose that damage to the bat wing, a physiologically dynamic membrane, brought about by G. destructans
is sufficient to directly cause mortality.
The potential homeostatic imbalance associated with the damage G. destructans
causes in bat wings warrants comparison to the electrolyte imbalance that occurs in amphibians infected by chytrid fungus (Batrachochytrium dendrobatidis
]. Recent studies demonstrated that infection by B. dendrobatidis
impairs the ability of frog skin to regulate hydration and homeostasis, causing electrolyte imbalance and ultimately cardiac arrest [49
]. Like WNS in hibernating bats, chytridiomycosis has caused precipitous declines among multiple species of wild amphibians. Additional similarities between skin infections of hibernating bats by G. destructans
and of amphibians by B. dendrobatidis
include the critical role the skin plays in the physiology of both hosts, as well as a lack of host inflammatory response to both cutaneous pathogens. The lack of inflammation in frogs is due to the superficial nature of infection. The lack of inflammation in bats is likely to be the result of natural downregulation of the mammalian immune system during hibernation [11
]. A dramatic difference between these host-pathogen relationships is the limited nature of epidermal invasion by B. dendrobatidis
in amphibians (Figure ) compared with the severe erosion, invasion and destruction of living tissues by G. destructans
(Figures and ).
Figure 3 Periodic acid Schiff-stained, 4-μm histologic section of skin from a lowland leopard frog (Rana yavapaiensis) infected with the chytrid fungus Batrachochytrium dendrobatidis. B. dendrobatidis (arrows) has colonized the superficial epidermal layer (more ...)
Despite the relatively minor visible changes associated with B. dendrobatidis infections, it is still a lethal physiological pathogen because of the role that the amphibian skin plays in the regulation of hydration and blood chemistry. We suggest that a similar, but less subtle, perturbation could be occurring in the wing membranes of bats with WNS. Damage to bat wings caused by G. destructans is often more extensive than can be appreciated with the naked eye. It took researchers decades to establish the causal link between skin infection by B. dendrobatidis and mortality in amphibians. A contributing factor to this delay was the challenge of demonstrating the potential significance of what appeared to be a superficial infection, and then documenting the magnitude of its physiological consequences. In addition, this novel fungal pathogen of amphibians belonged to a genus that was previously known only as a saprophyte that did not infect vertebrates - it was a new disease paradigm. Infection of bat wings by G. destructans, also a member of a genus typically defined as saprophytes, may similarly represent a completely new disease paradigm for mammals.
Answers to the relationship between skin infection by G. destructans
and bat mortality may be close to the surface. On the basis of available evidence and logical arguments, we have presented here numerous testable hypotheses for linking fungal infection of bat wings to WNS mortality. In summary, we hypothesize that G. destructans
may cause unsustainable dehydration in water-dependent bats, trigger thirst-associated arousals, cause significant circulatory and thermoregulatory disturbance, disrupt respiratory gas exchange and destroy wing structures necessary for flight control. A promising approach to a better understanding of WNS mortality might be to compare the North American disease to infection of bats by G. destructans
in Europe, where associated mortality is not apparent. If explanatory differences are not found between continents in the pathogen (for example, differences in fungal virulence) or environment (for example, the duration and severity of winters [9
]), then some of the host physiological or behavioral mechanisms we have outlined may help explain mortality in North American bats. Physiological differences between European and North American hibernating bats are unknown, but might include differences in host immune response [8
], differences in rates of cutaneous water loss (for example, differences in skin secretions, gland prevalence and structure), differences in the symbiotic organisms supported [9
], or differences in tolerance of dehydration or other physiological stress during hibernation. Host behavioral differences linked to physiology and potentially influencing the susceptibility of bats in different continents might include the size of groups formed [9
], the humidity and temperature ranges chosen for hibernation, typical activity levels (for example, foraging or drinking) during hibernation, or stereotyped responses to 'disturbance'. We urge further research into the physiological consequences of skin infection by G. destructans
and its impact on survival - with more than 150 years of detailed knowledge about the anatomy and physiology of bat wings, understanding the effect of WNS on bat wings seems tractable with available methods and expertise.