10/24/2012 - 16:06

The facts of fungi

Laura H. Kahn

Laura H. Kahn

A general internist who began her career in health care as a registered nurse, Kahn works on the research staff of Princeton University's ...

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It's the season for blood-sucking bats and flesh-eating zombies, but even the most ghoulish Halloween character can't hold a candle to one of the scariest life forms around: fungi.

As of October 15, the Centers for Disease Control (CDC) had received reports of 214 cases of fungal infections -- including 15 deaths -- across 15 states. At least two fungi have been found in contaminated preservative-free steroid injections: an Aspergillus species and Exserohilum rostratum, a cause of leaf spot disease. Thousands  of people may have been exposed to the meningitis-causing fungi when they received injections for orthopedic pain. The CDC is recommending antifungal medications to treat the meningitis, but months of treatment may be required: Severe fungal infections are very hard to eliminate. And, unfortunately, antifungal drugs usually have toxic side effects, including kidney damage.

Fungi can be found everywhere: soil, water, plants, animals, even in the air. They range from the familiar -- mushrooms, molds, mildew, and yeasts -- to the extraordinary, delicacies like truffles and morels. But others, like the appropriately named "Death Cap," are lethal. Fungi can cause significant illness and death in plants, insects, animals, and humans. They cause more diseases in crops than any other group of plant pests. In the late 19th century, a coffee rust fungus, Hemileia vastatrix, destroyed the coffee plantations in Ceylon (now Sri Lanka). This epidemic became the catalyst for a cultural touchstone: It was the primary reason why the British switched from coffee to tea. Then, during the 20th century, chestnut blight and Dutch elm disease decimated US chestnut and elm trees, forever altering the forests of North America. More recently, four newly discovered species of fungi have even been found to infect ants' brains in such a way that turns them into real-life zombies.

But fungi are also indispensible for healthy ecosystems, food production, biofuels, and medications such as antibiotics. We don't give fungi the respect they deserve, so research on fungi and fungal diseases are generally not a priority. Big mistake.

Fungi are integral to healthy ecosystems because they have the ability to decompose organic matter. They will eat anything -- even radiation. (There are fungi currently thriving at the Chernobyl nuclear disaster site.) Fungi absorb nutrients from their environment by growing hyphae into nearby materials and breaking them down with digestive enzymes. So most fungi are "saprophytes," feeding on dead or decaying matter, making them extremely important for composting and recycling. For example, the soft-rot fungus Trichoderma reesei is the culprit behind the destruction of military fatigues and tents in the South Pacific during World War II; but it also turns out to be a highly efficient producer of cellulase, an enzyme that breaks down plant-cell walls, which makes it highly useful in converting biomass -- like grasses, trees, and waste -- into biofuels.

We humans share a common ancestor with fungi: a single-celled organism that lived in the oceans around a billion years ago. Over 200 of the 1.5 million known species of fungi are associated with humans, either as part of the human microbiome or by causing human diseases. Some fungi even have the unusual ability to infect both plants and animals. For example, Aspergillus flavus, which produces the carcinogen aflatoxin, can infect both crops and people. What's more, fungi produce spores -- Mother Nature's bioweapons. Incredibly hardy, spores are able to disseminate via animals, water, or wind, spreading their decomposing ability far and wide. Wheat rust spores have been known to travel in the wind for more than 1,000 miles. Infection-spreading spores help explain why fungal diseases can quickly get out of control.

Rice blast. Hundreds of millions of people depend on rice as a staple food in their diets. Rice blast, caused by the fungus Magnaporthe oryzae, is found wherever rice is grown and is always a threat. Each year, rice blast destroys about 10 to 30 percent of the world's rice harvest. In 1995, an outbreak in Bhutan led to losses of more than 1,000 tons of rice, even though some of the rice plants under cultivation were supposed to have varying levels of resistance.

White nose syndrome. When pitted against fungi, bats lose. Since 2008, millions of beneficial insect-eating little brown bats have died from white nose syndrome, a fungal epidemic caused by Geomyces destructans, a European invader to North America. At one point, officials even feared that the bats would be wiped out completely, but so far a few tough survivors appear to be learning new survival strategies, such as keeping a distance from each other when they hibernate.

Contaminated steroid injections. This fall's meningitis outbreak has brought renewed attention to the dangers of fungi. How did this contamination happen? The likely cause appears to be a lack of oversight for the responsible compounding pharmacy. Compounding pharmacies mix up their own drug batches, charge less for their products, and avoid close FDA scrutiny. Products like medications for injection require special clean rooms and equipment to ensure sterility -- but without federal regulation, it's unclear whether the compounding labs in question were up to par. It doesn't help that the steroid vials did not contain an alcohol preservative, which might have reduced the risk of contamination. Understandably, there are now calls for greater oversight of compounding pharmacies.

Despite all of these threats, however, fungi are not all bad guys. A number of important medical therapeutics comes from fungi. We can thank mold for penicillin (Penicillium notatum), one of the first antibiotics, and for streptomycin (Streptomyces griseus). The primary metabolites of two fungi, Trichoderma polysporum and Cylindrocarpon lucidum, are responsible for a powerful immunosuppressive drug, Cyclosporin A, which is vital for preventing the rejection of organ transplants. And lovastatin, one of the first statin drugs used to lower cholesterol, is derived from the fungus Aspergillus terreus.

Fungi are ubiquitous and need far more study. In 2008, the American Academy of Microbiology issued a report, The Fungal Kingdom, recommending that a fungal census in the human microbiome and the environment should be conducted in order to better understand healthy humans and ecosystems. And the Institute of Medicine held a 2011 workshop on fungal diseases, concluding that surveillance of humans, animals, and plants at ports could be significantly improved to prevent the importation of potentially devastating fungal epidemics. These are good starts, but there is still much we don't know about these organisms. The recent outbreak of fungal infections and deaths illustrates that cutting corners comes with deadly risks. Horror scenarios are fine for movies, but let's avoid them in real life.