But during the next stage of the immune response, when lymphocytes should be activated, the fungus exerts its toxic effects. The investigators demonstrated that B. dendrobatidis cells and supernatants (the incubation liquid separated from the cells) impaired lymphocyte proliferation and induced cell death of lymphocytes from frogs, mice and humans. The toxic fungal factor also inhibited the growth of cancerous mammalian cell lines.
The toxic factor was resistant to heat and proteases (enzymes that cut proteins into pieces), suggesting that it is not a protein. It appears to be a component of the cell wall, because drugs that interfere with cell wall synthesis reduce its inhibitory activity and because the zoospore an immature form of the fungus that lacks a cell wall does not produce the factor.
The new findings suggest the possibility that toxic factors in addition to acting locally to inhibit the immune response might also get into the circulation and have neurotoxic effects, Rollins-Smith said.
"Fungal infection causes rapid behavioral changes frogs become lethargic and start to crawl out of the water suggesting that even though the fungus stays in the skin, the toxic material is having effects elsewhere."
The studies, led by graduate students J. Scott Fites and Jeremy Ramsey, could also suggest new conservation measures for species that may be medically important.
"Amphibian skin has long been favored in folklore for its medicinal properties," Rollins-Smith said. "Frogs are a rich source of potentially useful molecules that might work against human pathogens."
|Contact: Leigh MacMillan|
Vanderbilt University Medical Center