Category Archives: Microbes

Hospital bacteria: in my blood, in my IV.

I recently had a run-in with some bacterial cousins, courtesy of a small post-surgical wound. The bacteria were winning, so I spent a few days in the hospital where attentive medical staff mainlined antibiotics into my arm. The treatment worked, I’m all healed up, and the hospital guards set me free.

There were some interesting lessons in the wheeled tree of bags and bottles that was my shadow, my daemon, my constant umbilical companion.

IMG1107The molecules flowing into me were labeled and bar-coded. As was I. Both patient and bag were laser-scanned with every fresh dose of fluid. Just like the supermarket checkout: Beep-beep. And thereby, errors avoided, we hope.

But the names and numbers hid a deeper history. Each one of the antibiotics that I received was a synthetic derivative of a drug derived from a living organism. In other words, scientists took an antibiotic produced by a bacteria or fungus, then synthesized a new molecule that was modeled on the original chemical structure but with some extra added molecular tails and loops. Why bother with the modifications? Sometimes the synthetic version is more potent; sometimes it is a replacement for the original, a replacement necessitated by the evolution of antibiotic resistance in the pathogenic bacteria.

These drugs therefore belong to the second generation of antibiotics. The first generation were derived from other species, mostly from soil bacteria. These eventually lost their effectiveness as evolution did its work. The second generation of antibiotics take the original “scaffolds” or shapes, then tweak them to develop chemicals that are new, but not very different from the originals. This usually means that these second generation antibiotics have a limited lifetime of medical utility. The pathogenic bacteria, having found ways to dodge the first versions take little time to develop resistance to these new, rather similar synthetic versions. For drug companies working to make a profit, this is a bad investment strategy: why invest money and time developing products that will be useless, or nearly so, in the short or medium term? There is much more money to be made in convincing men that they need more testosterone. (The idea that the world might be better with a little less testosterone is unprofitable, it seems.) For the rest of us, none of this is good news. Bacterial evolution threatens to outpace the rate of development of new antibiotics.

I had the latest copy of Nature to keep me entertained during my stay and, by coincidence, it had a great article about a new avenue in drug development, an avenue that also promises to give us some fabulous insights into soil biology. Rather than move further down the path of synthetics, Ling et al., the paper’s authors, returned to the soil. Science’s initial foray into soil antibiotics was able to examine only one percent of the organisms that dwell in the soil. The other ninety nine percent died when brought into the lab. The first generation of antibiotics, in other words, was built on a tiny fraction of the soil’s potential pharmacopeia.

Instead of bringing soil to the lab, Ling’s team brought the lab to the soil. They buried a small “iChip,” a rectangular device filled with tiny bore holes, in the soil. The chip had previously been soaked in a diluted sample of soil. Bacteria colonized the holes and, because they were returned to their habitat in the soil, many of them thrived. Instead of one percent, the researchers managed to culture fifty percent of the soil microbes. Kaboom: That’s one small borehole for a bacteria, one giant leap for humankind.

Once the bacteria colonized and grew in the chip, they were presented with pathogenic bacteria like Staphylococcus aureus (“staph”) or Mycobacterium tuberculosis (“TB”). Using this method, Ling’s group discovered a new antibiotic that they named teixobactin. Importantly, this chemical is not structurally similar to existing antibiotics and the researchers have so far been unable to find any bacteria that can resist its attack. No doubt the same method will yield more drugs as we learn to converse with the mysteries of the soil. Excellent news indeed.

Surely it is time to honor the soil bacteria with little drawings of their habitats alongside the barcodes?

Nature News has an interesting commentary by Heidi Ledford, with photos, interviews, links, and technical details.

Hidden communities of fungi nestled within tree leaves

A maple leaf is more than it appears to be. Its substance is made not just from plant cells, but from a community of many species. “Maple” is in fact part plant, part fungus, part bacteria. Just as the human body is comprised of a vast “microbiome,” plants are also composite creatures.

To get a glimpse at this diversity, I cultured some of the fungal species found on and within the maple leaves growing on the tree by the front door.

To look at the fungi on the leaves’ surfaces, I dabbed maple leaves onto pertri dishes containing agar and fungus food, then waited a few days. Here is one such dish, displaying the diversity of species found on the leaf. Of course, many fungi don’t like petri dishes, so what we see below is a mere fraction of what is actually present on the leaf. The leaf itself is not so thickly coated; the petri dish gives fungi a place to grow and reveal themselves to our eyes.

maple_print

These fungi from the surface are a mixed bag. Some are potentially harmful to the leaf and will ultimately eat the leaf away when it drops in the autumn. Others are likely protective or live as commensal squatters. Some feed on the droppings of caterpillars or the honeydew of aphids. A few might have drifted from the humans, goats, and stacked firewood below.

To peek at fungi that live inside the leaf, “endophytes,” I sliced some leaves into tiny pieces, sterilized their surfaces, then placed them onto petri dishes. Compared to the leaf “prints” taken from the surface, it took a couple of days longer for these endophytic fungi to appear on the dishes, but they too showed quite a diversity of forms. Here are two examples:

Maple_endoMaple_endo2To make sure that I was not simply growing fungi that were wafting in the air or present on my forceps, I also ran some “control” plates which yielded either nothing at all or a few white blobs.

How endophytic fungi interact with tree leaves is largely unknown. But one of their roles is protective, secreting substances that deter the growth of pathogenic fungi. For example, endophytes isolated from Douglas maple release a chemical that poisons a variety of nasty plant diseases.

Interestingly, endophytes in sugar maple leavs seem to be more diverse in old growth forests than they are in younger, managed forests, or in urban areas. But these are preliminary findings. We have only the haziest understanding of the ecology of the fungal world hidden within leaf laminae.

Inside each leaf: a whole community. Within the community: hundreds of stories waiting to be heard. One story is clear, though: if we believe that creatures — humans included — live apart from “the other,” we’re deluded.

Lyme disease, foxes, and coyotes

A gray fox swaggered across University Ave this morning, its bushy tail bouncing as it trotted. It was headed to the patch of woodland behind Otey Parish Hall and the Duck River Electric building. I’ve seen fox scat on the road there, so I think this must be a resident, perhaps the same animal that I saw last summer with a rabbit in its mouth.

This has been a busy few months for fox and coyote sightings in Sewanee. Now, a paper in the Proceedings of the National Academy of Sciences has added some insight into the tangle of interactions among these wild dogs and their prey. Apparently, tick abundance and Lyme disease risk is affected by the numbers of foxes and coyotes. The paper examines data from the northeast, but its results may also be relevant here.

Lyme disease (caused by the bacteria Borrelia burgdorferi) is transmitted to humans by tick bites (especially bites from nymphal stage of Ixodes scapularis, the black-legged tick) But humans are not the main host of these ticks, so the abundance of ticks is determined by the abundance of their other mammalian hosts, especially mice. Foxes and coyotes both prey on mice, so you’d think that more foxes and more coyotes would mean fewer mice, and therefore fewer ticks, and therefore fewer Lyme disease cases. But things are not quite so simple.

The abundance of foxes is indeed correlated with a decreased risk of Lyme disease. Foxes love to eat mice and fox populations can get quite dense, so mice fare poorly in areas with healthy fox populations. Coyotes also eat mice, but coyotes live at lower population densities than foxes. Coyotes also drive out foxes. So the overall effect of coyotes on Lyme disease is a positive one: more coyotes = fewer foxes = more mice (despite the few that get eaten by coyotes) = more ticks = more Lyme disease. And deer? There was no correlation with Lyme disease; mouse abundance drives the dynamics of the disease and deer abundance seems to have little effect (except in areas that have no deer — an unusual situation these days — that do have lower incidences of Lyme).

Excerpt from one of the paper’s figures, showing correlations (or lack thereof) between Lyme disease and either coyotes per fox (positive correlation), foxes (negative correlation), or deer (no correlation).

An important caveat: this paper examined correlations among estimates of the abundance of different animals. But correlations are slippery things. They seem to imply that we’ve discovered a cause-and-effect relationship, but this is often misleading. So I’m sure this story will evolve as scientists tease out the subtleties (does the effect of foxes depend on the availability of other prey?) and alternative explanations (might some unknown causative third variable be correlated with coyotes and Lyme?). I wonder how domestic cats play into all this. They are major predators on mice and often live at densities well above what could be supported without the subsidy of store-bought cat food. Do they also suppress Lyme?

Some notes for blog readers in the south:

1. We’re well outside the “hotspot” of Lyme disease, as shown on this CDC map. The disease does not seem to be increasing in many parts of the south. But, in Virginia and other areas that are close to the center of Lyme’s activity, the disease is increasing quite rapidly.

2. The south is blessed with other tick-borne diseases. Southern Tick-Associated Rash Illness is one; Rocky Mountain Spotted Fever is another.

3. Although we do have black-legged ticks here, lone star ticks and dog ticks are more common. These are not prime carriers of Lyme, but they can transmit the other tick-borne diseases.

For more info about ticks, the CDC site has some good links and great pictures (which will make your skin crawl). Obviously, if you have medical concerns about a bite, check in with an MD, not a Rambler.

Three-way partnership = bad news for a two-by-four

This old piece of pine lumber (the stub end of a two-by-four) has been devoured by termites. The rest of our garage has been spared their attentions, so far.

A weighty block has turned to crumbly paper. The insects responsible for this impressive work were scurrying nervously in the too-bright light of day, each one looking like a fat grain of rice from a milk pudding. Add sugar and I’m ready to become an myrmecophage (yes, anteaters love termites).

Termites are like cows, they graze on plant material that is completely indigestible to them. Only by harboring an internal band of helpers can termites (and cows) free the nutrients and energy locked in woody tissues. The termites’ helpers are in the hind part of the gut. Here single-celled protists (relatives of “amoebae”) engulf small wood particles and digest them. But these protists are cows too…they have within their cells a peculiar group of bacteria, the critters that do the actual work of making wood-destroying enzymes. So helpers live within helpers.

The fact that only a few obscure groups of bacteria can digest cellulose (the main component of “wood”) explains a lot about our world. If more creatures could digest wood, then trees likely could not exist (their trunks would be gobbled up in short order), wooden structures would last about as long as gingerbread houses (which are, I’m told, digestible, explaining perhaps their limited popularity outside of confectioners), and our great stockpiles of coal (old compressed wood) would not exist. No forests, no houses, and no industrial revolutions (at least not coaly ones…and what other kind has there been?).

Lynn Margulis: an appreciation

Our experience of the world is mediated through stories. Stories (also called theories by those who need a patina of scientific respectability) tell us how the world came to be, how it works, and what its fundamental rules are. Once is a while, someone comes along who so fundamentally changes the nature of our guiding stories that our life experience is transformed. Lynn Margulis, who died two days ago, is such a person.

Margulis taught us the importance of symbiosis in biology — the union of two or more different species into a new form. Her views were dismissed, ridiculed, and ignored for years. Finally, some of her ideas prevailed, although she continued to receive sniper fire for her penchant for questioning dogma.

Now, thanks largely to her, we understand that every living species is, at some level, the result of symbiotic fusion and union: all animal, plant and fungal cells have ancient bacterial cooperators hidden within; trees are united to fungal helpers below-ground; the animals that build coral reefs cannot survival without algal partners; insects are partly nourished by symbiotic gut bacteria; and even DNA itself appears to jump among species, intertwining radically “different” species into new entities. These processes happen in every part of life’s delta, but are particularly powerful among Margulis’ favorite creatures, the so-called “microbes” (the true “99%”).

Our metaphors have to shift. The “tree” of life? No, life has too many cross-connections among distant branches. An unstable, flowing delta is a better image. Evolution as a capitalistic competition among individuals? No, there are as many unions as robber barons; self-interested cooperation is rife.

As a small homage to Margulis, here are some of my DNA sequence data from the mitochondria of land snails. These are the color-coded “letters” of the DNA alphabet found within the ancient bacteria that live inside every cell in a snail’s body. But this description is misleading: the bacterial cells truly don’t “live inside,” instead they have melted their bodies into the other, creating an individuality-destroying symbiosis. Thank you, Lynn Margulis.

Each row is the DNA from one individual. Each column is one position along the DNA stand. The different "letters," A, T, C, and G, are color-coded.

For more on Margulis’ life, see John Horgan’s blog entry at Scientific American. He has some nice insights. The NY Times has a shorter obituary.