XB-ART-59924
Philos Trans R Soc Lond B Biol Sci
2023 Jul 31;3781882:20220133. doi: 10.1098/rstb.2022.0133.
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Amphibian infection tolerance to chytridiomycosis.
Grogan LF
,
Mangan MJ
,
McCallum HI
.
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Animal defences against infection involve two distinct but complementary mechanisms: tolerance and resistance. Tolerance measures the animal's ability to limit detrimental effects from a given infection, whereas resistance is the ability to limit the intensity of that infection. Tolerance is a valuable defence for highly prevalent, persistent or endemic infections where mitigation strategies based on traditional resistance mechanisms are less effective or evolutionarily stable. Selective breeding of amphibians for enhanced tolerance to Batrachochytrium spp. has been suggested as a strategy for mitigating the impacts of the fungal disease, chytridiomycosis. Here, we define infection tolerance and resistance in the context of chytridiomycosis, present evidence for variation in tolerance to chytridiomycosis, and explore epidemiological, ecological and evolutionary implications of tolerance to chytridiomycosis. We found that exposure risk and environmental moderation of infection burdens are major confounders of resistance and tolerance, chytridiomycosis is primarily characterized by variation in constitutive rather than adaptive resistance, tolerance is epidemiologically important in driving pathogen spread and maintenance, heterogeneity of tolerance leads to ecological trade-offs, and natural selection for resistance and tolerance is likely to be dilute. Improving our understanding of infection tolerance broadens our capacity for mitigating the ongoing impacts of emerging infectious diseases such as chytridiomycosis. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.
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GO keywords: immune response
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Figure 1. Example of evidence for variation in tolerance to chytridiomycosis. (a) Fitness (measured as days survived post-exposure) against pathogen burden (measured as the natural logarithm of the zoospore equivalents [zse] load measured via skin swab qPCR at day 28 post-exposure for all individuals, chosen to avoid confounding from mortality) regression lines separated by population (Eucumbene, Grey Mare, Kiandra and Ogilvies) for the alpine tree frog (Litoria verreauxii alpina). There was a significant interaction (varying regression slopes) between zse and population via ANCOVA. (b) Survival curves for the same animals from (a), separated by population. Note the long subclinical period prior to mortality (clinical signs only manifest in the last 12–48 h prior to mortality). Importantly, the infection loads at time of death ranged up to 8 million zse in this species. Data sourced from Grogan et al. [19]. |
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Figure 2. Example of epidemiological and ecological implications of infection tolerance to chytridiomycosis. (a) In the rainforests of eastern Australia, the tadpoles of the Fleay's barred frog (Mixophyes fleayi) act as a tolerant reservoir, maintaining an environmental zoospore pool year-round causing high-exposure risk within the stream (represented in red). As these tadpoles metamorphose, many are expected to die from chytridiomycosis (unpublished data; [37]), while those that survive disperse from the stream, potentially spreading infection to naïve catchments due to their long subclinical period (unpublished data). Adults are exposed to infection as they come to the stream to breed, with males maintaining territories along the stream year-round [38]. Eggs are initially naïve to infection, but the tadpoles soon become infected after hatching. (b) Hypothetical depiction of changes in life-history-related exposure risk independent of seasonal temperature changes (red lines, separated for adults into females [solid line] and males [dashed line]), resistance (orange line), tolerance (violet line) and mortality probability (black line) throughout the course of an individual amphibian's lifespan. Ecologically, the high-exposure risk at the stream combined with very low tolerance and resistance at metamorphosis results in high mortality of the metamorphosing amphibians, leading to a likely life stage bottleneck (unpublished data; [37]). |
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Figure 3. Example of leveraging components of resistance and tolerance in a species under pathogen pressure. The critically endangered spotted tree frog (Litoria spenceri) continues to decline throughout its range in southeast Australia, in large part due to pathogen-mediated competition from syntopic reservoir hosts such as the stony creek frog (L. lesueurii) [93]. Here, we demonstrate hypothetical results of leveraging tolerance (host mortality rate due to Bd) and multiple facets of resistance (transmission rate, recovery rate) in improving conservation outcomes of a species under strong pathogen pressure from the amphibian community. In all panels, various two-species, stage-structured, SI compartmental models were run from quasi-equilibrium to characterize 20-year outcomes for L. spenceri adults sharing a zoospore pool with a population of L. lesueurii. (a) Median (±95% bootstrap confidence interval) of L. spenceri adult density after 20 years of implementing varying interventions across 1000 equilibrated parameter sets. At intermediate values, reduced mortality due to Bd (tolerance) more efficiently rescues L. spenceri populations than equivalent reductions in transmission rate. Doubling the recovery rate from infection offers only marginal benefits without concomitant changes in transmission or reductions in mortality. (b) Heatmap comparisons of 20-year L. spenceri outcomes in two dimensions, increasing recovery rate by 0–100% of its baseline value while decreasing mortality due to Bd and transmission rates from 100% to 0% of their baselines. Black stars indicate the original model (without parameter modifications, from field-realized parameter estimates) in each panel. Combined reductions in Bd-associated mortality and transmission offer the strongest population outcomes for L. spenceri. (c) The three-dimensional relationship across varying levels of Bd-associated mortality, transmission and recovery rates, where the barrier density plane represents the median 20-year adult density of L. spenceri across all scenarios. High-density outcomes of L. spenceri fall below the plane, while low densities are represented above the plane. |
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Figure 4. Example classification tree demonstrating the evolutionary implications of the long subclinical period. The alpine tree frog (Litoria verreauxii alpina) provides an important case study when considering the potential evolutionary implications of the long subclinical period of chytridiomycosis. In this system, adults return to waterbodies to breed, rapidly become infected via the environmental zoospore pool and generally breed successfully, before the majority of them go on to perish [94]. Here, we have an example of where selection via differential reproductive success fails to occur in the breeding cohort due to the long subclinical period. In this system, the age structure has been dramatically truncated, with the majority of breeders not surviving past their first season [95,96]. In the laboratory, this species is highly susceptible, demonstrating 98% mortality across individuals sourced from four populations (n = 277; [19]). While some animals no doubt survive their first breeding season (potentially due to qualitative resistance or temperature-mediated cures) and might be expected to drive selection in subsequent breeding seasons for any traits they together possess, their genetic contribution to future generations is considerably weakened by the presence of successful offspring from the rest of their cohort that ultimately succumbed to infection. |
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