The thick yeasty capsids (coats) of Cryptococcus gattii relative C. neoformans. C. gattii also has a thick capsid. CDC/Dr. Leanor Haley

It’s not every day you read about suggestions for potential health-related travel advisories to U.S. states. But such is the case for the Pacific Northwest, where an emerging fungal infection has — very unusually for fungi — begun felling otherwise healthy people. A growing number of cases of the potentially fatal disease cryptococcosis have been diagnosed in people who merely traveled to Washington, Oregon, or British Columbia.

There are several very scary things about this fungus, but foremost among them is that it a) was introduced somehow from the tropics, most likely South America/Brazil or also possibly Africa and is somehow not finding it a problem to survive in Canada; b) is actively spreading up and down the Pacific Northwest coast; c)hangs out in the environment, where it can get along apparently fine without us (and seems to particularly like the bark of and soil around trees like Eucalyptus); d) is acquired from the environment, that is, you don’t have to have contacted with an infected person or animal; e) doesn’t manifest itself symptomatically for 2-12 months after one picks it up and e) can kill otherwise healthy people.

So let’s review. This means that you can just be hiking along in the woods, minding your own business, and a few months later you’re dead. Now I’m not saying this is *common*. Only 200 people have been seriously affected in 10 years. And let’s face it, there are a lot of other things that can kill you while hiking along minding your own business, much, much quicker and more commonly than these fungi: bears, mountain lions, lightning, exposure, rockfalls, your own stupidity, deranged axe murderers, errant militias, etc. But the very fact that, like anthrax, you can pick it up for no apparent reason from the environment, and much more easily, is disturbing. (Histoplasmosis is also picked up by inhalation but it is well known you must spend time around bird or bat droppings. Aside: can you think of any other diseases that are picked up just by inhalation from the wild?)

This particular organism is Cryptococcus gattii, a relative of the Cryptoccoccus neoformans that gained some fame in infecting AIDS patients when the immune disease emerged in the ’80s. Cryptococcosis begins as a lung infection, but can progress to meningitis. C. gattii, a cousin of C. neoformans, first emerged on Vancouver Island in 1999, but in the last few years, two new strains have emerged that seem to be killing otherwise healthy people in numbers much higher than earlier strains.

There are anti-fungal drugs that can help show C. gattii the door, but the wikipedia article for C. gattii contains this ominous sentence:

Antifungals alone are often insufficient to cure C. gattii infections, and surgery to resect infected lung (lobectomy) or brain is often required.

Resectioning *brain*??! Oh hell no.

Fortunately, infection with this organism remains relatively rare, but that’s no guarantee of safety. Why? This fungus is having sex. And that is one possible origin of the two newly virulent strains that have emerged in the Pacific Northwest — and possibly the source of future, more dangerous strains. It is also possible that the two new strains were newly introduced from their tropical diversity centers. But the scientists *know* there’s a lot of C. gattii hanky-panky going on. They looked at a couple dozen genetic markers in this recent PLoS study, and compared which isolates had which markers and how they were organized in the genome. They also tried to reconstruct the evolutionary and geographic relationships between various North American isolates using these data. They found huge genetic diversity among their isolates, and that at least one north American strain came from Australia. They also that the fungus is bumping up its numbers by quick and easy asexual reproduction.

But the initial creation of the new hyper-virulent types, they concluded, was likely due to sex. Only sexual reproduction provides the opportunity for lots of large-scale genome reorganization; that’s one of sex’s main advantages. When two entire genomes get together, a process called “crossing over” takes place that allows all the various chromosomes to swap corresponding bits. The result is sometimes good, sometimes bad, but whatever the outcome, generation of diversity and evolution often happen a heck of a lot faster per generation with sex than without.

Lest you think that’s the only worrying bit, it turns out that this fungus has a rather kinky sex life. Not only is it having sex with all the other mating types (fungi often have many “genders”, which for convenience scientists refer to as “mating types”), it can also, somewhat unusually for fungi, have sex (and I mean produce viable offspring) with its own type, a process called unisexual mating. Sheesh.

So that’s what was chiefly covered in the news reports. But it turns out there’s more to this story. Because this fungus is actually a yeast — an infectious yeast. Now I know what you may be thinking: yeast are the source of everything good and worthy on Earth: fresh, crusty, heavenly leavened bread, wine, beer, soy sauce, etc. And you’re right. But that doesn’t mean there aren’t evil yeast. Nasty yeast. Parasitic yeast. Because “yeast” is a lifestyle, not a taxonomic group or single species.

The yeast you’re probably most familiar with, Saccharomyces cerevisiae, commonly called baker’s yeast, is but one fungus that has adopted this way of life. And that way of life is: forsaking multicellularity for swingin’ single cellhood. In a way, yeast have devolved (although that’s a bit misleading; it doesn’t mean they’re less adapted or successful than they were before; just that being unicellular is more like their long-ago ancestors). The standard fungal body plan today is a multicellular filament, or tube. The tube branches, and the collection of branched tubes makes up the fungal body, or cottony “mycelium” we are familiar with from the surface of refrigerator contents gone rogue. Yeast are fungi that have given up this form, and have gone back to single celled living, a bit like a protist. It would be as if all your spleen cells decided that they’d rather just go off and live on their own in pond water — they’re sick and tired of cleaning up your bloodstream, thank you very much! — and they want out of the cooperative.

But it gets more complicated than that. Some fungi can go back and forth between their normal, filamentous lifestyle and the yeast lifestyle. Histoplasmosis, mentioned earlier, can do this. In the wild, it is a brownish mycelium that lives in bird droppings and bat guano. Once inhaled and installed in your lungs, it becomes a yeast. Cryptococcus neoformans and Cryptococcus gattii are among this group too. Sometimes they are filamentous. Sometimes not.

And here’s where it gets really weird. Because yeast is a lifestyle, not a taxonomic group (like a genus or family), yeast come from all over the fungal family tree. Baker’s yeast is an ascomycete like morels and truffles. But C. gattii is . . . a yeast evolved from the jelly fungi! Jelly fungi are super-awesome amazing organisms in the basidiomyctes (a major division in the fungi, like ascomycetes, that make their sexual cells on special pronged cells called basidia) that usually decay wood and produce fantastically fun-to-touch-and-play-with fruiting bodies that are gelatinous and sometimes quite colorful.For reference, here is what one looks like:

Ascocoryne sarcoides, Photo by Daryl Thomas, Mushroom Observer. Creative Commons Attribution-Unported 3.0 license

The jelly fungus you might be familiar with, if you are familiar with one at all, is the wood ear mushroom*, Auricularia auricula, commonly used in Asian cuisines — in particular, in hot and sour soup. Again, these fungi are perfectly innocuous. Some fungi produce very different forms when they live asexually or sexually. Because they’re so different, mycologists often give the sexual form a different name from the asexual form (an explanation of whether this is a good idea and why mycologists continue the practice could take up a book). The sexual jelly fungus form of C. gattii is Filobasidiella bacillispora, although it’s not necessarily the case that the jelly form would produce a structure big enough for you to see with your naked eye. I know of no jelly fungi that can hurt you either by touch or consumption. But the yeast form of these particular fungi apparently can. Weird!

A larger question might be: what are these fungi doing in us? Are they only accidental parasites? What are they doing out in the wild when they aren’t infecting us? As they say . . . further studies are needed.

But in the meantime, the weirdness parade goes on. C. gattii has *also* been isolated from a regular menagerie of other mammals, including koalas, llamas and. . . are you ready for this? . . . dolphins. How dolphins managed to spend time frolicking in the woods (or how the fungus managed to spend time frolicking with dolphins) is a subject for another blogger.

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*According to the Wikipedia article, the Japanese name for these jelly fungi is “tree jellyfish”(!) Sometimes literal foreign phrases smack you upside the head with a perfectly obvious insight you never thought of before.

Byrnes, E., Li, W., Lewit, Y., Ma, H., Voelz, K., Ren, P., Carter, D., Chaturvedi, V., Bildfell, R., May, R., & Heitman, J. (2010). Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States PLoS Pathogens, 6 (4) DOI: 10.1371/journal.ppat.1000850

Klebsiella sp. are flagellum-less, rod-shaped, Gram-negative bacteria. The Gram state of a bacterium has to do with the  properties of its outer coating; Gram-positive bacteria have a membrane surmounted by a thick outer wall made of peptidoglycan that readily takes up purple Gram stain, while Gram-negative bacteria have a thin peptidoglycan cell wall sandwiched between inner and outer membranes. Knowing the Gram-state of bacteria helps microbiologists sort out what kind of bacteria they might be dealing with. That’s helpful, as you can imagine, when many of your subjects are simple balls (cocci) or rods (bacilli) that look more or less the same.

The funny name comes from a 19th century German microbiologist named Edwin Klebs. The group is in the enteric bacteria, which itself is within the Gamma-purple bacteria. Misleadingly, many purple bacteria are not purple. But they are bacteria. Tricky, I know. That’s probably why the group seems to have acquired a new name: Proteobacteria. See if you can find it on the bacterial family shrub.

As implied by the term enteric bacteria, many are found in the gut of animals, but many others roam wild and free. Like Klebsiella, they’re all Gram-negative rods, but some do have flagella. Enterobacteria contain some famous names indeed: Escherichia, Shigella(a maker of dysentery), Salmonella, Proteus, Klebsiella, Enterobacter, Erwinia(a plant pathogen that causes fire blight in apples and pears and soft rots in vegetable crispers around the world), and Yersinia, one species of which (Y. pestis) made it big as bubonic plague (aka The Black Death). There are others, too. Though Klebsiellas are sometimes human pathogens, some strains live happily in your gut or on your skin, and many others thrive in the environment and may never see a human their entire lives.

There are presently about seven species of Klebsiella known, and they are becoming important as hospital-acquired (nosocomial) infections. Now we don’t know what species was in the tobacco the researchers studied — they only narrowed it to genus with their genetic screens. Perhaps many species in this genus were present. But take note of the final sentence from this WebMD article about Klebsiella pneumoniae:

Infection with Klebsiella organisms occurs in the lungs, where they cause destructive changes. Necrosis, inflammation, and hemorrhage occur within lung tissue, sometimes producing a thick, bloody, mucoid sputum described as currant jelly sputum. The illness typically affects middle-aged and older men with debilitating diseases such as alcoholism, diabetes, or chronic bronchopulmonary disease. This patient population is believed to have impaired respiratory host defenses. The organisms gain access after the host aspirates colonizing oropharyngeal microbes into the lower respiratory tract.

Campylobacter "twisted bacterium" sp. I need quotes around my middle name. Note the stringy flagella. U.S. Agricultural Research Service

Not long after I became a health and environment reporter in Wyoming, I was assigned to cover a smokeless tobacco talk given by a scientist from the Mayo Clinic.

Smokeless tobacco (aka moist tobacco,  chewing tobacco, and spit tobacco), he said among other points, supported huge populations of live bacteria.

That was surprising to me. I’d never thought about it before, but it did make sense. The tobacco companies don’t exactly autoclave their product.

Since it was my job to report on the talk, I reported that the substance was “teeming with bacteria”, a statement I felt was amply supported by the evidence presented by this guy.

The next day I got a call from a scientist at a state university in the south. He said he was calling to correct what he claimed were the inaccuracies in my story. He then proceeded to enumerate my alleged errors. I clearly remember him singling out the “teeming bacteria” statement.

“Come on,” he said.

For those of you not in the United States, the Mayo Clinic is one of the top, if not the top, medical centers in the country. And though the Mayo Clinic scientist backed up my reporting on his talk when I subsequently called (and the story was just about his talk — not an attempt at a broader survey of the science, even if the southern scientist’s points had been backed up by a broader literature), I felt stung, to be sure. The Gulf Coast scientist even went so far as to send me some of his papers supposedly disproving what I’d written. It was all rather odd. I ask you, why would a scientist at a university 1,000 miles away go out of his way to call a reporter at a circulation 18,000 paper in Wyoming to correct alleged errors that in no way mentioned his research? How would he even know about the story?

Well, guess what? It turns out that not only is smokeless tobacco teeming with live bacteria, so are dry cigarettes, according to a recent article in Science News (see also here for an earlier article). Scientists have found genetic markers for hundreds of species in cigarettes, and have cultured several of them out of packages purchased off the shelf.

When cultured with blood, some of these bacteria can digest it. And as the article points out, scientists have long known smokers have higher rates of lung infection. Doctors always assumed that was due to immune system suppression. But inoculating your lungs with bacteria or their spores several times a day probably doesn’t help.

In retrospect, it’s not surprising. You take leaves. You hang them up in a moist, dark, warm place (a tobacco barn). You wait. In plant pathology, we called this a moist chamber*. It’s how we coaxed fungi to fruit so we could grab their spores for pure culture. Bacteria seem to like the treatment too: scientists found Campylobacter, Clostridium, Corynebacterium, Klebsiella, Staphylococcus, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherischia coli, and Bacillus subtilis signatures in cigarette tobacco, according to the Science News article. Not only is this a who’s who of the pathogenic human bacteria world (although is should be noted many species in these genera are not pathogens under ordinary circumstances), these and other bacteria are responsible for producing the most potent carcinogens in cigarette smoke — nitrosamines — when they start chowing down on tobacco leaves. Nor is this the first time cigarettes were found to be hosting . . . er . . . organisms. Cigarettes are often contaminated with plant viruses too. Though entirely harmless to humans, it’s been known for years that people who’ve handled cigarette tobacco can transmit  tobacco mosaic virus.

Now don’t get me wrong — the presence of some bacteria is no reason not to eat or drink a food. Trust me, practically everything you put in your mouth has bacteria in it or on it. Even freshly cooked food probably has a few bacteria or fungal spores settle on it between the pot and your plate. And we purposely introduce billions of “good” bacteria and fungi into food all the time. If you’ve been reading this blog long enough, you know I’d be just as likely to say yogurt, your kitchen sponge, and your mouth are teeming with bacteria (which they are). This story does make me wonder, however, if tea leaves experience something similar to tobacco leaves during processing. Does anyone know? But you don’t smoke tea, and the products of bacterial action on yogurt and tea leaves don’t give people cancer. Tobacco bacteria do.

Next time: a closer look at Klebsiella.

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*Now that I think about it, I think we used grow lights over most of our moist chambers. But I don’t think dark would necessarily discourage fungi.