Amphibian killer forces immune-cell suicides

A skin fungus that has swept around the globe killing frogs and their relatives can make key players in amphibian immune systems kill themselves.

The fungus nicknamed Bd (for Batrachochytrium dendrobatidis)has flummoxed biologists because the little skin bumps it causes in susceptible amphibians look inconsequential. Yet this member of the chytrid fungi can kill a wide range of animals, some within days.  

Part of Bd’s power comes from compounds in its cell walls that disable amphibian immune cells called lymphocytes and trigger these cells to self-destruct, says Louise Rollins-Smith of Vanderbilt University in Nashville. These fungal substances can withstand heat, acid and a protein-smashing enzyme, Rollins-Smith and her colleagues report in the Oct. 18 Science.

Cells of many kinds carry built-in systems for do-it-yourself breakdown, known as apoptosis. Bd’s fungal walls “seem to be especially effective at asking the lymphocytes to commit suicide,” Rollins-Smith says.

This discovery starts to clarify how Bd creates its unexpected dangers. “Amphibians have a great immune system,” she says. “They’ve evolved with fungi and should be able to recognize it and clear it.” Yet descriptions of fungal attacks have noted that even severe skin infections of Bd often trigger little or no inflammation.

The normally responsive amphibian immune system, much like the human one, has layers of defenses. Specialized cells pick up signs of trouble and signal the lymphocytes. Receiving the alarm, lymphocytes recognize the menace and call in a range of other cells that actually kill the invaders. It’s this lymphocyte calling-in-soldiers step that Bd foils.

“Bd is an elegant pathogen in so many ways,” says veterinarian Rick Speare of James Cook University in Townsville, Australia, who in 1993 was one of the first researchers to observe a massive frog die-off in the wild. The new paper may not immediately lead to new therapies, he says, but it’s “highly significant” for understanding how the disease progresses.

To study this early phase of infection, Rollins-Smith and her colleagues exposed cells from two frog species to fungi and their fluids. The initial infection-spreading cells of the fungus, called zoospores, swim by lashing a hairlike flagellum and don’t have a cell wall. And they don’t have much effect on frog lymphocytes, the researchers found.

But once these mobile cells settle onto skin, they give rise to structures covered with complex cell walls. Alive or dead, these walled fungal cells (and even their fluids) can kill lymphocytes that would normally proliferate when mixed with an invader.

Exactly what’s in the disabling brew remains a puzzle. And so does the defensive biology that allows some amphibian species to thrive despite fungal attacks. African clawed frogs, the source of some of the lymphocytes that died in the lab tests, usually survive the fungus in the wild. Rollins-Smith speculates that their success may come from a different kind of immune defense: small peptide molecules in frog skin mucus known to have protective effects.

Editor’s Note: This story was updated on October 28, 2013, to clarify the number of frog species studied.