The second most studied creature

kw: book reviews, nonfiction, microbiology

The most studied creature is, of course, the human animal, ourselves. The second most is a much smaller item indeed: Escherichia coli. Adult humans mass sixty to a hundred kilos; an individual E. coli bacillus masses one or two trillionths of a gram (1-2 pg, pg=picogram).

These E. coli colonies in a petri dish were sent by NASA aboard the Genesat satellite experiment in December, 2006. In his new book Microcosm: E. coli and the New Science of Life Carl Zimmer doesn't mention Genesat, but he discusses just about everything else regarding this little bug. A few highlights:

• Every human carries from a few grams to a kilo or so of them in our colons. At a trillion cells to the gram, they number a hundred to a thousand times the number of humans on the planet—in each of us.
• The number of human cells in a typical human is less than ten trillion.
• The prevalence of E. coli in experimentation is mostly because they are one of the easiest organisms to grow in large quantities.
  
• A well-fed colony of E. coli can double in mass every thirty minutes. Given food enough and a sufficiently "swirly" mixing environment, a single cell could thus grow to equal the mass of the earth in just 66 hours, or less than three days.
• A number of terrible disease-causing bacteria that were once given names such as Shigella, have now been found to be strains of E. coli. The O157:H7 strain is a fearsome beast, one of the "flesh-eating" bacteria. You can't use antibiotics against it, because the toxins released during its death throes kill the host (you, if you're infected!).
  
• Relatively cheap insulin is just one product used by millions, that is now produced almost exclusively by genetically engineered E. coli, grown in huge vats.
  

This bit of time-lapse imagery shows initially three cells on the verge of dividing. Decoding the times, successive images were taken after 12, 17, 33, 80, 97, 109, 115, and 179 minutes. By 97 minutes each original cell has become four, and several of them are about ready to divide again. By the end of the series (179m = 3h), they are getting hard to count; I make out 54.

The images are phase-contrast micrographs and if your monitor's resolution is 100dpi (4 lpmm), the magnification is nearly 1000x. These are pretty good images for a light microscope. Without phase contrast, the cells are nearly transparent, though with dark-field illumination they aren't hard to see. I don't have a phase-contrast setup, but I do have dark-field capability.

This 2000x image (somewhat greater than 3000x in the larger image you get by clicking) is about the best you can see E. coli using light. Better resolution requires an electron microscope...not to be found in any homes I know of!

Carl Zimmer's emphasis is on the history and sociology of this bug, so he doesn't have the gallery of photos one might imagine. He does have a compelling series of chapters that outline the way this amazingly versatile critter works...to the extent that it is known to date. He clearly makes the point that E. coli is far from a "primitive germ": it is the product of four billion years of evolution, just as we are, a very sophisticated generalist of a germ. It lives not only in the human gut, but in the gut of every warm-blooded animal on Earth. And that is just the "mostly harmless" strains (though fearsome O157:H7 lives in farm animals, it doesn't harm them...not them). Other strains are found in "external" environments worldwide. It can live with our without oxygen, at a wide range of temperatures, and it can feed on quite a variety of organic chemicals in addition to its favorite sugars.

It is the first prokaryote ("pre-nucleus") to be shown to engage in a single-celled version of sex. So promiscuous is it on that it exchanges DNA with quite a variety of bacterial species, to the point that there is a serious effort to redefine "species" for prokaryotes. DNA-trading, both voluntary through "conjugation" and involuntary due to viral activity, causes a huge amount of "horizontal" gene flow throughout the whole microscopic domain.

Perhaps this very promiscuity is the safeguard that keeps our engineered strains of E. coli from going wrong and screwing up our world. They've already figured out, billions of years ago, how to share genes in every direction without screwing up their world. We get a free ride. And this same promiscuity has made them the ideal Frankenbugs: it has become almost easy and quite cheap to coerce them into bearing and expressing almost any gene we like...with a big proviso.

Sugar. Eukaryotes ("good nucleus" – all life bigger than bacteria) have developed ways of decorating proteins with sugar groups, which changes how they fold up. This is essential for making many proteins work right. Prokaryotes (so far as is known) don't add sugars, so much work is being done to either teach them the trick or to modify them to use extra amino acids with sugars pre-attached. We were lucky that insulin doesn't need to be glycosylated (sugar decorated) to work.

There is no single photo that shows everything about the bacterial cell. For one thing, E. coli looks different depending on its environment. This cell (magnified ~10,000x) is in a social mood, ready to bind to others to form a biofilm. Isolated cells going about their own business don't have these pili (hairs).

Do you know what a biofilm is? The next time you floss your teeth (you do floss, don't you?), take a second to look at the whitish goo that was between your teeth. Dentists call it "tartar". It hardens into "plaque", which has to be removed with a dental pick. Both tartar and plaque are biofilms, and there is no safe, chemical way to remove them. Floss and dental-picking are the only known methods.

Perhaps you have a plastic shower curtain that never quite dries out at the bottom, and it's getting slippery. I do. That slippery film is a biofilm. The buildup of "stuff" on the surface of a porcelain sink, that you need to use cleanser and a sponge to remove, is a biofilm. Bacterial cells have settled down, linked together a lot like locking arms, and excreted starches and sugars to hold them to the surface and shield them from enemies and chemicals. Biofilms are probably the normal mode of life for most bacteria; the single ones we see illustrated in textbooks and encyclopedias were on the move, getting ready to settle down.

But illustrations such as this painting, composed of information gleaned from numerous images, help us see what the cells look like. The trailing strands are flagella, which the cell forms as needed when it must travel. When the critter settles down, it sheds its flagella

The colors in this image are fanciful, shown only to enable easier grasp of details. The only colors present in real E. coli cells are the creamy or golden yellow seen in colonies like those shown in the first image above. There is so little color in a single cell that under the microscope they look clear or slightly grayish, like elongated drops of water...very small drops.

One final thought I find fascinating. A single strain of E. coli has a genome consisting of between 4,000 and 6,000 genes (maybe a wider range than this). Some strains have as many as 1,000 genes not found in any other strain, and some share fewer than 2,000 genes with the "pangenome" of E. coli, the total collection of all known E. coli genes, which numbers nearly 20,000 to date. As it happens, there is every likelihood that the E. coli pangenome is greater than the human genome. Now that is both exciting and scary. But I also wonder, are there genes that some people have and not others...and how extensive is the human pangenome?