As microbiologist Hazel A. Barton of Northern Kentucky University descended into the cool, damp, pitch-black darkness of an abandoned iron mine in Pennsylvania, she switched on the LED lamp on her helmet just as she had hundreds of times before and prepared to take stock of another subterranean ecosystem. But she started getting an uneasy feeling that something wasn’t right.
“It’s hard to describe,” Barton says. “But it felt evil.”
As she continued into the mine, last worked a century ago, Barton realized her premonition was right. Everywhere she looked, bat bodies were covered with white fungus. “The bats flying around were zombies,” she says. “On the cave floor, there were hundreds of bat carcasses. Because they decompose quickly, there were piles of bones with loose flesh. In some places, it was just a brown, sludgy mass.”
It turns out that the fast-spreading fungal disease, named white-nose syndrome for the visually striking white Geomyces destructans fungus seen on the muzzles of afflicted bats, had taken hold in the mine. White-nose syndrome has killed more than 1 million hibernating bats in caves and abandoned mines in the U.S. during the past four years, an annihilation that is being called the worst die-off of wildlife in North American history.
Despite their poor public image, bats are essential: They consume vast numbers of insects, some of which are destructive to crops and carry human diseases, and they help pollinate plants and spread seeds. White-nose syndrome is threatening regional extinction of some bat species, which could have far-reaching consequences for agriculture, forestry, human health, and natural ecosystems that depend heavily on the creatures of the night.
Because of these irreplaceable benefits, federal and state agencies and private institutions, led by the U.S. Fish & Wildlife Service (FWS), have developed a coordinated national management plan. Officially unveiled on Oct. 28, the plan provides a framework for developing solutions, including many that draw on chemistry, to help protect bats and eradicate the fungus without damaging the environment.
Scientists still have more questions than answers about white-nose syndrome, says wildlife biologist Jeremy T. H. Coleman, FWS’s national white-nose syndrome coordinator. “We aren’t certain if the fungus is the primary cause of the disease or if it might be an opportunistic secondary effect of some other pathogen,” Coleman says. “We don’t know how easily the fungus is spread between bats. We don’t know how persistent the fungal spores are or how many spores are needed to get a foothold on a bat.”
The white-nose syndrome outbreak began in early 2006 in a cave west of Albany, N.Y., Coleman says. It spread rapidly throughout the northeastern U.S. and north into Ontario and Quebec in Canada. The disease has been observed in all six species of hibernating bats that live in the northeastern U.S.; there are 45 species of bats in the U.S., about half of which rely on hibernation for winter survival. The fungus is threatening important bat habitats in Kentucky and Tennessee, and it has been detected as far west as Missouri and Oklahoma.
White-nose syndrome causes uncharacteristic behavior in bats in winter months, including flying outside during the daytime and clustering near the entrance to hibernation sites where it is colder, Coleman explains. The fungus damages bats’ skin, especially wing membranes, which are important not just for flying but also for controlling water balance and blood pressure.
The restless behavior could be caused by dehydration or by irritation stemming from the fungal infection, he says. The behavior could also be because of mycotoxins produced by the fungus—ergot fungus on grains, for example, produces alkaloids that affect the human circulatory system and can cause hallucinations and irrational behavior.
No matter the cause, the result of this restlessness is that diseased bats appear to use up their fat reserves too quickly and are unable to survive winter, Coleman says. Bat colony losses in some locations have reached 75–100%, he states.
As a first line of defense, federal and state agencies are encouraging recreational cavers to stay out of caves and abandoned mines. They are also asking commercial cave operators and administrators of caves in national parks and national forests, which have fewer bats because of the regular influx of human visitors, to develop white-nose syndrome education programs to inform the public about the disease. FWS has also issued federal guidelines, based on work by Barton’s group at Northern Kentucky, for preparing and using decontamination solutions to help halt human spread of the fungus.
“It’s hard to knock out the spores, because they are designed to spread the fungus in the environment,” Barton notes. “We developed an extensive list of agents that work well to inactivate spores, some of them gleaned from microbiologists’ experience with bacterial spores such as anthrax. But most of the chemicals on the list aren’t safe for general use without training and are harmful to the environment. So we came up with some off-the-shelf alternatives.”
For example, Barton’s team developed decontamination solutions using household chemicals, such as ammonium-based Lysol brand disinfectant, and procedures to treat clothing and equipment after cave visits. Lysol has historically been used in decontamination efforts—famously during the Spanish flu pandemic in 1918—and it’s effective against G. destructans spores, Barton says.
Meanwhile, scientists are starting to pull together data that can be used to combat white-nose syndrome. On one research front, microbiologist David S. Blehert of the U.S. Geological Survey’s National Wildlife Health Center, in Madison, Wis., led a team that first isolated the fungus from bats and used DNA analysis to identify it as a new species of the common Geomyces soil fungus (Science 2009, 323, 227). The fungus, which the researchers named G. destructans because of its devastating effects, thrives in cool, humid conditions characteristic of caves and mines that bats frequent and hibernate in.
G. destructans has been observed in Europe for several decades, Coleman notes, but without the associated collapse of bat colonies. He says it’s possible that the fungus was introduced to the U.S. by someone who visited caves on both continents. The lack of mortality in European bats could be because of different environmental conditions, evolved resistance among European bats, or minor genetic mutations in the fungus leading to greater virulence in U.S. strains, he adds.
Blehert and coworkers shared their data with geneticist Christina Cuomo and coworkers at the Broad Institute, a joint Harvard-Massachusetts Institute of Technology research center that’s home to an initiative aiming to sequence fungal pathogens of medical, ecological, or agricultural importance. In quick order, Broad researchers sequenced and assembled the genome of G. destructans, which they announced and publicly released on Sept. 16.
“The genome should rapidly advance our understanding of this pathogen,” Cuomo says. “The hope is that the genome will be a platform to jump-start work on this problem, to help devise ways to track and combat this fungus.”
“We can now begin to mine the genomic data to identify potential toxin production genes or other virulence factors,” Blehert adds. Scientists also can begin to look in detail at the similarities and differences between North American and European isolates of G. destructans, he says.
Several research groups have conducted preliminary lab and field studies to test the efficacy of commercially available fungicides and other possible agents against G. destructans, Coleman says. For example, at an American Society for Microbiology meeting in Boston on Sept. 12, Vishnu Chaturvedi, director of the microbiology laboratory of the New York State Department of Health’s Wadsworth Center, reported data on a high-throughput screening of 2,080 compounds, including drugs, natural products, and known biocides, as potential fungicides against six strains of G. destructans. Chaturvedi and his colleagues previously studied the biology of the fungus (PLoS One 2010, 5, e10783).
Chaturvedi says the fungus is most susceptible to common azole-based fungicides, such as ketoconazole, itraconazole, and fluconazole, the active ingredients found in over-the-counter jock itch, yeast infection, and athlete’s foot creams and dandruff shampoos. The fungus is also susceptible to amphotericin B, a cyclic polyene natural product drug used against life-threatening fungal infections.
“There are many steps before an agent that inhibits fungal growth in the lab can be used to effectively treat this disease,” Barton points out. “We need a fungicide that can be dissolved in something that won’t harm bats, can be applied without people touching the bats, needs only be applied once to avoid continually disturbing the bats, works at cool temperatures in hibernation sites, and won’t harm other fungi or wildlife in the environment.” There are also downstream impacts to consider—for example, many cave-based aquifers supply drinking water to people, she says.
Barton notes that zoologist DeeAnn M. Reeder’s group at Bucknell University has tested some commercial fungicides on bats in the lab and found that they almost exclusively “outright kill the bats.” Besides that, most of these fungicides are approved for human topical uses and not as environmental-control agents, she says. Therefore, they can’t be used for white-nose syndrome without Environmental Protection Agency approval, which would require costly and time-consuming toxicology studies and environmental impact statements.
“If we use natural compounds not restricted by EPA, it may be possible to move more quickly while limiting toxic impacts on bats and other organisms,” Barton suggests. In one example, Barton’s research team is testing spearmint oil, which contains the terpenoid carvone. The spearmint extract is volatile, so it can be administered as a vapor that can waft over hibernating bats, she explains. In just-completed lab tests, carvone is effective against both the fungus and the spores, she says. The team is now set to start field trials.
Coleman agrees that a traditional chemical treatment in a natural cave may never be possible. “There are just too many nontarget species,” he says. Coleman imagines that if white-nose syndrome continues to progress, scientists may consider “captive holding,” in which bats are caught and held in a secure location that can be kept free of the fungus, such as old mines, ammunition bunkers, or other constructed sites.
Bats can live up to 20 years, Coleman says. But because hibernating bats typically have one pup per year and the mortality rate of the young bats is moderate, bat numbers don’t fluctuate widely over time, he notes.
“Populations of bats affected by white-nose syndrome will not be able to recover quickly,” he observes. “With the decimation so far, there is definitely going to be some loss of genetic diversity. We haven’t yet crossed a threshold where we might have irreparably lost any species. But it could be coming soon.”
To evaluate how bats might fare long-term against the fungus, a team led by ecologist Winifred F. Frick of the University of California, Santa Cruz, and Boston University analyzed population data collected during the past 30 years from cave and mine hibernation sites throughout the northeastern U.S. (Science 2010, 329, 679). By combining the data with population models, the researchers determined that one of the most common bats in North America, the little brown bat, likely will become extinct in the affected area within 16 years if white-nose syndrome continues unabated.
Similarities between white-nose syndrome and other recent animal and plant declines in which fungal infections appear to play a role—such as those affecting frogs, honeybees, sea turtles, and aspen and bristlecone pine trees—are worrisome, Coleman says. These outbreaks, along with the influx of invasive plant and animal species, may be becoming more prevalent because of social and economic globalization and possibly warmer global temperatures, he says.
“As scientists, we’re not fortune-tellers trying to say bat extinction is a foregone conclusion,” Frick says. But the bat decline and the model projections portend the seriousness of the problem. She adds that often with diseases resistant individuals emerge that buy scientists more time to solve a problem such as white-nose syndrome. “We’ve got to learn more about what’s happening before we can come up with solutions of how to stop it,” Frick says.