Mysterious Fungus Threatens Frogs

Frog species around the world are going extinct. Perhaps more than 100 species have perished since 1980 and more than 400 are suffering rapid and massive die-offs according to one estimate (EcoHealth 2007, DOI: 10.1007/s10393-007-0093-5).

Climate change, habitat loss, and invasive foreign species are among the culprits fueling the devastation. But just one is paving the path to extinction for as many as 200 frog species: a fungus known as Batrachochytrium dendrobatidis or Bd.

During the past decade, researchers have made promising strides toward understanding this deadly organism, but Bd is still considered an emerging and mysterious pathogen. Researchers are now focusing on the biochemistry behind Bd infections to better protect frogs and amphibians worldwide.

Among Bd’s biggest secrets is how it kills frogs. “We know very little about the molecular and chemical interactions between the hosts and the pathogens,” says Erica Bree Rosenblum, an evolutionary biologist at the University of California, Berkeley.

What is known is that the fungus infects amphibians through their skin. Mobile, fungal precursors called zoospores latch onto an animal’s exterior and begin to grow. As the spores mature, they sprout germ tubes that can tunnel into amphibian skin cells. The developing fungi produce their own zoospores, which are eventually released—either directly into the frog to further the infection or into the environment to spread the disease.

But that’s far from the whole story. Sophisticated though their asexual onslaught may seem, fungi typically do not pose threats to frogs.

“Amphibians have very competent immune systems,” says Louise A. Rollins-Smith, an immunologist at Vanderbilt University. “You would think that Bd is just a skin pathogen; the frogs should recognize it and clear it. It turns out the fungus has some capability of fighting back.”

How Bd suppresses a frog’s immune response remains largely unknown. When it comes to this topic, Rollins-Smith has written what many in the field consider to be the benchmark study, which is less than a year old (Science 2013, DOI: 10.1126/science.1243316). Bd unleashes a chemical inhibitor that goads the amphibian’s lymphocytes—the cells responsible for attacking intruding microbes—into apoptosis, or cellular suicide.

Although the researchers concluded the molecule Bd uses to cripple a frog’s immune response is not a protein, they don’t yet know what it is. “We’re working as hard as we can to find out what it is that we’re missing,” Rollins-Smith says.

She suspects that a carbohydrate on Bd’s cell wall is the inhibitor. Although experiments have ruled out common fungal cell wall components like chitin and β-1,3-glucan, the carbohydrate theory is being bolstered by a recent report Rollins-Smith helped author (Nature 2014, DOI: 10.1038/nature13491).

In the study, researchers killed Bd by flash-freezing it in liquid nitrogen, which Rollins-Smith says should leave the carbohydrates of the fungal cell wall intact. Scientists then exposed frogs to the dead fungus and found that it triggered an immune response, meaning the hosts still detected the pathogen. The frogs ramped up lymphocyte production in their spleens, but the dead Bd was unable to sabotage this process, leaving the animals better prepared to fight future infections. Thus, dead fungus could potentially help protect frogs from living Bd.

“The new study is an exciting prospect, at least in a clinical setting,” says Jamie Voyles, an ecologist at New Mexico Institute of Mining & Technology who studies diseased amphibians in the field. “It’s an exciting proof of concept.”

But others aren’t as optimistic. At UC Berkeley, Rosenblum studies the genes of both frogs and Bd. She notes that some frogs are extremely susceptible to infection whereas others are not. Some Bd strains are lethal, whereas others are less deadly. Researchers have yet to find genetic markers that reliably tag certain frogs as easy targets or certain fungi as adept killers.

So therapies may be limited by scalability, Rosenblum suggests. What works for one frog species or Bd strain may not work for another. Then there’s the additional challenge of scaling up to treat a global problem.

Rosenblum does not foresee the Bd epidemic ending anytime soon.

“This is a long slope of death we’re walking,” she says. “How well will amphibians survive?”