Epidermal epidemic: unravelling the pathogenesis of chytridiomycosis

Abstract

Chytridiomycosis, a lethal fungal skin disease of amphibians, fatally disrupts ionic and osmotic homeostasis. Infected amphibians increase their skin shedding rate (sloughing) to slow pathogen growth, but the sloughing process also increases skin permeability. Healthy amphibians increase active ion uptake during sloughing by increasing ion transporter abundance to offset the increased skin permeability. How chytridiomycosis affects the skin function during and between sloughing events remains unknown. Here, we show that non-sloughing frogs with chytridiomycosis have impaired cutaneous sodium uptake, in part because they have fewer sodium transporters in their skin. Interestingly, sloughing was associated with a transient increase in sodium transporter activity and abundance, suggesting that the newly exposed skin layer is initially fully functional until the recolonization of the skin by the fungus again impedes cutaneous function. However, the temporary restoration of skin function during sloughing does not restore ionic homeostasis, and the underlying loss of ion uptake capacity is ultimately detrimental for amphibians with chytridiomycosis.

Mechanistic basis for loss of water balance in green tree frogs infected with a fungal pathogen

“…For epithelial junction-associated genes, we observed an upregulation of mRNA expression for claudins 4 and 15 and e-cadherin, which are responsible for establishing the barrier function of the epithelium and regulating paracellular salt and water movement (29). The increase in junctional protein gene expression may be a response to compensate for the loss of skin integrity in Bd-infected frogs, as seen in Gauberg et al (27) and Wu et al (80). However, changes in mRNA expression alone do not necessarily reflect commensurate changes in the abundance of the functional protein, nor do they directly pertain to changes in protein activity levels (57,63,80).…”

“…The increase in junctional protein gene expression may be a response to compensate for the loss of skin integrity in Bd-infected frogs, as seen in Gauberg et al (27) and Wu et al (80). However, changes in mRNA expression alone do not necessarily reflect commensurate changes in the abundance of the functional protein, nor do they directly pertain to changes in protein activity levels (57,63,80). To support a mechanistic hypothesis and ascribe a functional significance to the observed changes in mRNA abundance, future studies should look to measure abundance changes directly at the level of the protein.…”

“…Because these osmoregulatory hormones also influence water regulation by the skin, kidney, and urinary bladder (31), plasma osmolality and muscle water content may be transiently improved through the activity of other osmoregulatory organs. Nevertheless, sloughing provided only a temporary normalization of water balance, and within 36 h of sloughing, infected animals were exhibiting signs of hyponatremia (71,80).…”

“…This work also identifies potential mechanisms contributing to the loss of osmotic homeostasis during Bd infection in frogs, including an increase in net cutaneous water efflux and disrupted osmotic balance, despite an increased mRNA expression of skin junctional proteins. The cumulative effects of increased rates of water loss (62), increased skin permeability (27,80), and increased sloughing frequency (78) may further accelerate disease progression in Bd-infected frogs. Importantly, these results help us understand the dynamic interplay between the host's compensatory responses and the costs associated with disease progression in the context of disease-associated mass extinctions.…”

In vitro modeling of Batrachochytrium dendrobatidis infection of the amphibian skin

“…Both pathogens parasitize amphibians by colonizing the keratinized layers ( stratum corneum ), resulting in disturbance of skin functioning and possibly leading to death in these animals [4, 6–10]. Whereas Bsal induces the formation of skin ulcera [5], Bd typically induces epidermal hyperplasia, hyperkeratosis and increased sloughing rates, eventually leading to the loss of physiological homeostasis (low electrolyte levels) [11–18]. The worldwide distribution of chytridiomycosis, its rapid spread, high virulence, and its remarkably broad amphibian host range lead to considerable losses in amphibian biodiversity [1].…”