It emerges that a fungal infection killing salamanders has many potential reservoirs, and that environmentally resistant spores transmit disease. Urgent interventions are needed to save susceptible populations from extinction. See Letter p.353
Emerging infections caused by fungi are contributing to biodiversity loss1. Although the number of fungal species that inhabit Earth is unknown, estimates2 range from 1.5 million to 5 million, and it seems reasonable to assume that a deep pool exists of pathogenic fungi that have previously undiscovered epidemiological traits. Accidental introductions of fungi to non-native habitats are an unfortunate by-product of the intensification of global trade in forestry, agriculture and wildlife species. Through trade, a group of fungi known as the amphibian-parasitizing chytrids have invaded ecosystems worldwide3. On page 353, Stegen et al.4 present an analysis of factors affecting the pathogenicity and transmission of one such fungus, Batrachochytrium salamandrivorans, which can wipe out salamander populations.
When a previously unknown fungus is identified as the cause of a disease outbreak, urgent research is required into the pathogen's biology to understand the disease-causing mechanisms and to determine how to control the organism. In the 1979 science-fiction film Alien, the heroine Ellen Ripley combats a 'perfect pathogen' which combines an unholy trinity of epidemiological features that lead to local extinction of the host: high virulence, no host immunity against the pathogen and an environmentally resistant transmission stage. Similarly, a previously unknown 'alien' fungus called B. salamandrivorans (Bsal)5 invaded northern Europe from Asia around 2010 (ref. 6). The fungus had extraordinarily high virulence, killing more than 96% of infected fire salamanders (Salamandra salamandra) at the first recorded fungal outbreak site in the Netherlands7. Stegen and colleagues describe the suite of epidemiological traits that enabled Bsal to be a successful perfect pathogen during its invasion of the Robertville forest in Belgium, 57 kilometres from the initial outbreak site.
Following the first observations of fire-salamander deaths from fungal infection in Robertville in 2014, the authors continuously monitored these amphibians as infection spread through the population. Their observations make grim reading. Salamanders had a 33% probability of becoming infected across 10-day monitoring intervals, and infected animals had only a 13% chance of surviving for longer than 10 days. The infection disproportionately infected sexually mature animals, which contact each other through social interactions, and the population collapsed to only 10% of its original size within 6 months of the arrival of the fungus. Two years later, less than 1% of the fire salamanders had escaped infection to roam the forest, which was almost emptied of their species.
The authors made many key epidemiological observations that help to explain the outbreak's ferocity. Bsal recovered from salamanders two years after the onset of the outbreak was as lethal in infection trials as the initial Bsal isolate, indicating that the fungus was not evolving towards lower virulence, which can happen when trade-offs occur as hosts and pathogens co-evolve8. To test whether salamanders could generate a protective immune response, the authors conducted cycles of experimental inoculation of fire salamanders with Bsal followed by antifungal drug treatment. The efforts to generate immunity were to no avail. The experimental animals all died, and it seems reasonable to infer that wild animals that escaped the initial outbreak have no immune defence against the pathogen.
Another study9 found that expression of immune-system genes increases when Tylototriton wenxianensis salamanders are infected by a fungal relative of Bsal known as Batrachochytrium dendrobatidis, whereas infection of these salamanders by Bsal did not increase their expression of immune-system genes. This suggests that Bsal has evolved properties that dampen the host immune response.
High virulence and lack of a salamander immune response alone would not account for the outbreak's severity, so Stegen and colleagues searched for factors that might enable high rates of fungal transmission. They looked for, and found, reservoirs of infection by analysing the forest soil for DNA traces of Bsal. The fungus might therefore be able to survive and remain infectious for long periods outside its host. This hypothesis was confirmed when the authors observed that an uninfected salamander could be infected by contact with soil that an infected fire salamander had contaminated. Contamination probably occurred through the shedding of fungal spores.
Notably, the authors demonstrated that environmental persistence was explained by the presence of a previously unknown type of resilient and non-motile thick-walled Bsal spore, which has unique characteristics that promote its survival. These fungal spores, known as encysted spores, are protected by a thick, water-repellent cell wall. They can float at the interface between air and water, rather than having the active swimming behaviour found in another type of Bsal spore, known as a motile zoospore. The Bsal encysted spores probably help extend the infectious lifetime of the fungus, because encysted spores had a substantially higher survival rate than the motile zoospores when exposed to microscopic pond predators known as zooplankton. The authors tested whether encysted spores could adhere to the feet of waterfowl and found that they could. This might mean that birds disperse Bsal into previously uninfected and distant populations, perhaps explaining the extraordinarily rapid spread of the infection (Fig. 1).
Stegen et al. also searched for non-salamander reservoirs of infection that could be intensifying the outbreak. Previous experiments6 suggested that the Bsal host range was limited to newt and salamander species. Stegen and colleagues found that the frog species Alytes obstetricans (the common midwife toad) could be infected by the fungus and transmit the disease to salamanders. Infection of the alpine newt Ichthyosaura alpestris, which shares the forests with the salamanders alongside A. obstetricans, revealed that the newts could develop chronic Bsal infections. These newts showed little evidence of acquiring protective immunity against pathogen re-infection, which indicates that they too are natural reservoirs for this pathogen.
As Stegen and colleagues mention, the combination of multiple susceptible hosts and a virulent and environmentally persistent pathogen seems to create a 'perfect storm' of infection that has led to the almost complete destruction of fire salamanders in the populations infected so far. Their observations are consistent with a model of Bsal dynamics in which infectious spores build up in multiple reservoirs across the timescale of an outbreak, creating a highly infected ecosystem. More must be done to try to conserve fire salamanders and other susceptible amphibian species that have restricted ranges and are under direct threat of extinction from Bsal. It should also become a priority to try to prevent introductions of other non-native pathogenic chytrids because, despite decades of research, no effective method has emerged to reduce their effect in the field10. It is currently unclear how Bsal can be combated in the wild beyond establishing 'amphibian arks' to safeguard susceptible species as the infection marches relentlessly onwards. Clearly, scientists, policymakers and citizens have much to do if we are to help Europe's salamanders weather this perfect storm. Footnote 1
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