By Roberta Attanasio
Frogs and other amphibians – salamanders and caecilians – have been declining worldwide during the past few decades at an alarming rate. According to a June 2012 assessment by the International Union for the Conservation of Nature and Natural Resources (IUCN), about 41 percent of amphibian species are at risk of extinction, and some are already extinct.
Like many other inhabitants of our planet, amphibians have been hit hard by climate change and habitat loss – and not only. Amphibians have also been decimated by the spread of chytridiomycosis, which is defined by the IUCN as the single most devastating infectious disease of vertebrate animals. In a historical article published in 2008, David Wake and Vance Vredenburg state: “A general message from amphibians is that we may have little time to stave off a potential mass extinction.”
The deadly chytridiomycosis is caused by Batrachochytrium dendrobatidis (Bd), a fungus found on all continents except Antarctica. According to epidemiological evidence described in an article published in 2004, the Bd fungus was present in African clawed frogs (Xenopus laevis) in their native South Africa as early as the mid-1930s. African clawed frogs infected with Bd do not show any clinical sign of disease and can carry the fungus for long periods of time without dying. Therefore, these frogs are Bd carriers and transmit the fungus to vulnerable species.
Worldwide dissemination of Bd started in the 1930s because of the international trade of African clawed frogs. From the 1930s to 1950s, large numbers of these frogs were caught in the wild in southern Africa and exported across the world, mostly for use in the first human pregnancy tests and scientific research. Results from a study recently published in the journal PLOSone confirm that Bd was present as a stable, endemic infection in Xenopus populations in Africa prior to their worldwide distribution, which likely occurred via international live-amphibian trade. Vance Vredenburg, lead author of the study, said: “Today, these frog populations are often found in or near urban areas, probably because hospitals released them into the wild when new pregnancy testing methods were invented in the 1960s.”
Bd proliferates in skin cells and rapidly kills amphibians by disrupting skin function – it impairs the skin’s ability to absorb electrolytes. A few years ago, a group of scientists from Australia found that, in diseased frogs, the skin’s ability to take up sodium and potassium ions from the water decreases by more than 50 percent, leading to a sharp decline of these ions in the blood and eventually causing cardiac arrest and death.
Despite these recent discoveries, there was an unanswered question: “Why is the amphibian immune system so inept at clearing the fungus?” Now, a team of investigators from Vanderbilt University reports, in an article published in the journal Science and entitled “The Invasive Chytrid Fungus of Amphibians Paralyzes Lymphocyte Responses” (October 18, 2013), that Bd paralyzes the immune system of the affected amphibians by releasing a toxic factor.
The researchers found that white blood cells called macrophages and neutrophils, which are responsible for the first line of immune defenses, are not affected by the toxic factor. However, the toxic factor inhibits the proliferation of other types of white blood cells called lymphocytes. In addition, the toxic factor induces lymphocyte cell death. Lymphocytes are responsible for the adaptive function of the immune system, which is essential in protecting against infections when the first line of defenses are not sufficient to control the spread of micro-organisms. Because of lymphocyte loss, frogs are unable to eradicate Bd before it induces irreversible damage to their skin.
Results of the study suggest that the toxic factor is not a protein, as it is resistant to heat and to the action of proteases (enzymes that cut proteins into pieces). However, drugs that interfere with cell wall synthesis reduce the killing of lymphocytes. In addition, the zoospore — an immature form of the fungus that lacks a cell wall — does not produce the toxic factor. Thus, the toxic factor is likely to be a component of the fungus cell wall.
Louise Rollins-Smith, senior author of the study, said: “The new findings suggest the possibility that toxic factors — in addition to acting locally to inhibit the immune response — might get into the circulation and have neurotoxic effects. 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.”
For the past few years, researchers have been trying different approaches to treat existing Bd infections, as for example administering anti-fungal drugs to tadpoles or using “probiotic” bacteria that naturally secrete anti-fungal compounds. However, albeit a leading one, Bd is only a contributor to the global decline of amphibian population.