Published online 22 October 2009 | Nature | doi:10.1038/news.2009.1031

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Fatal frog fungal disease figured out

Electrolyte imbalance stops amphibians' hearts.

frogFrogs are suffering from a fatal fungal infection.Vance T. Vredenburg/SFSU

A fungal infection that is killing amphibians around the world acts by disrupting the flow of electrolytes across their skin, ultimately causing heart failure. The discovery is helping to raise hopes that a treatment for the infection could one day be given to amphibians in the wild.

Batrachochytrium dendrobatidis, a kind of chytrid fungus that causes the skin disease chytridiomycosis in amphibians, was likely spread around the world by the South African clawed frog (Xenopus laevis) in the 1930s and 1940s, when the frog was widely used as a pregnancy test. A pregnant woman's urine, injected under the frog's skin, would contain sufficient hormones to make the animal ovulate.

But although the South African clawed frog seems to have immunity to the disease, many other amphibians are not so lucky. According to one study led by chytrid expert Karen Lips of the University of Maryland in College Park, chytridiomycosis can kill 80% of amphibians in one year in an area with cool, moist conditions.1 Until now, no one was sure exactly how the fungus killed its victim; some researchers thought that it might secrete a poison.

Jamie Voyles, a disease ecologist at James Cook University in Townsville, Queensland, Australia, and colleagues exposed Australian green tree frogs (Litoria caerulea) to the fungus, and have now worked out its deadly mode of attack.

Voyles and colleagues monitored the progression of the infection, took blood and urine samples and measured electrolyte flow across skin samples. They found that levels of two ions — potassium and sodium — were greatly reduced in infected frogs, and that the ability to move these ions back and forth across the animals' skin had been greatly impaired.

"Frog skin is really unique because it is permeable to water but it must maintain proper concentrations of these [electrolyte] ions," says Voyles. In infected frogs, "the electrolyte balance is all out of whack".

The low potassium levels, in particular, were probably responsible for a breakdown of the electrical regulation of the heart, and the frogs ultimately died because their hearts stopped. The work is reported in Science2.

Rich solution

The team found that an electrolyte-rich solution, similar to sports drinks but more concentrated, delayed death in infected frogs. But it couldn't cure them. "Because the skin is damaged, we can't really keep them from dying unless we fix the problem in the skin," says Voyles.

Although captive frogs can be bathed in an antifungal medicine to rid them of their infection, there is no easy way to treat the hundreds of species of wild amphibians at risk of being wiped out by the fungus.

Voyles's work is just one piece of research that might someday lead to a treatment that could be deployed in the wild. Geneticist Erica Rosenblum of the University of Idaho in Moscow is looking at gene expression in both the fungus and the host to determine what makes the fungus so lethal — and why amphibian immune systems don't seem to be aware of the infection.3 "Jamie has found that their osmotic regulation is all screwed up, they are essentially having heart attacks," she says. "Mine is an earlier question: why don't they have an immune response?"

One possible treatment is being pursued by Reid Harris, a microbial ecologist at James Madison University in Harrisonburg, Virginia. He has found that at least some species of amphibians have beneficial bacteria on their skin that produce a protective antifungal agent.4 He is looking into the possibility of adding more of these bacteria to the soil in ecosystems where vulnerable amphibians live, to boost their natural defences. "People are already doing this in their gardens and larger-scale agricultural applications as well," he says.

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Harris would first like to try the technique on populations of frogs in captivity — so-called survival assurance colonies held in zoos and other institutions awaiting the day when they can be safely returned to the wild.

Despite all these advances, Lips says that she has seen too many frog populations destroyed by the fungus to retain her optimism about saving what is left. "I don't know that there is enough money going to the right labs quickly enough to make a difference," she says. "More governments and NGOs need to step up. I mean, we are losing half the amphibians on the planet. And throwing amphibians into zoos is a short-term solution. It doesn't solve any problems." 

  • References

    1. Lips, K. R., et al. Proc. Natl. Acad. Sci. USA 103, 3165-3170 2006 | Article | PubMed | ChemPort |
    2. Voyles, J. et al. Science 326, 582-585 (2009).
    3. Rosenblum, E. B. et al. PLoS ONE 4, e6494 (2009).
    4. Harris, R. N., Lauer, A., Simon, M. A., Banning, J. L. & Alford, R. A. Dis. Aquat. Organisms 83, 11-16 (2009).
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