Wednesday, February 23, 2011

Caulobacter Crazy (Anti-) Glue

There are few things as annoying as out-of-control glue. Klister is one example—it gets everywhere. In violin-building, I use hide glue which is difficult to control for another reason: it is only sticky for a few minutes, which gives you very little time to get your work done. Ideally, glue should only stick when and where you want it.

The wonderful glue used by Caulobacter is amazing not only for its strength, but as we’ve recently found, it can actually be turned off pretty simply. This surprising discovery suggests that Caulobacter may have a more complicated social life than previously thought.

To begin with, I have to show you the canonical Caulobacter picture, from the lab of Yves Brun:

This is a picture that, for a while, seemed to be featured in every single paper and talk on the organism. It shows the “life cycle” of Caulobacter: it starts out (on the left) as a freely-swimming single cell. If it swims to a nice place, it sheds its flagellum, and grows that famous stalk and holdfast. Once anchored, it grows and divides, giving birth to a new free-swimming cell. Only the anchored cells divide, and once they’ve anchored, they never move again. So, as long as there is sufficient food, they’ll crank out swimming cells; when conditions turn bad, they are doomed.

Caulobacter, like a lot of bacteria, will form fairly dense growths of cells on a surface—a so-called biofilm. All the cells in a Caulobacter biofilm are growing on stalks, anchored by that marvelous glue—I can picture wandering through such a film, like wandering through a forest of oddly shaped trees that occasionally give birth to flagellated blobs. If conditions are good in this biofilm forest, then it’s advantageous for the newly-hatched Caulobacter swimmers to immediately stop swimming, grow a holdfast, and settle right in place—and so they do. The Caulobacter doesn’t fall far from the tree--sometimes they even cling to each other.

However, if times are tough, all the food has been used up and there are predators around, the existing Caulobacter might wish to urge their offspring to move on a bit before they settle down. A group of researchers, led by Yves Brun, found that this is exactly what happens: distressed Caulobacter biofilms produce something that essentially keeps Caulobacter glue from sticking.

There are several examples of Bacterial cells communicating with members of the same species using a variety of small molecules, so Brun set to work to figure out what Caulobacter used. Surprisingly, the molecule that inactivates Caulobacter glue is Caulobacter DNA. Brun found that a lot of cells in a stressed-out biofilm die, and shed their DNA into the area—and this DNA specifically interacts with the newly-formed holdfast of a former swimming cell, and completely turns off the glue.

Brun was commendably thorough in trying to prove that this was really happening. Unlike other known chemical signals used by Bacteria, the DNA didn’t trigger any changes in gene expression—so it wasn’t the case that the DNA stopped production of the glue: it inactivated the glue that was already there. His group purified large quantities of Caulobacter holdfasts, and found that the DNA only attached to the sticky end of the holdfast. The DNA didn’t interact with any other part of the cell. So, it seemed that the DNA from dead Caulobacter cells was a very specific “anti-glue.”

Here’s the really weird bit: only Caulobacter DNA was effective as an anti-glue. They tried DNA from other organisms; they tried DNA from distant and near relatives of Caulobacter—and only Caulobacter DNA was effective as an anti-glue! Some close relatives’ DNA could slightly reduce the glue’s effectiveness—but not as effectively as Caulobacter.

This is a real puzzle, and as yet there’s no satisfactory explanation. This is a glue that can stick to glass, plastic, rock, metal, you name it. Brun’s group tried DNA with the same overall chemical composition—the same percentage of G:C bases as Caulobacter—and got nothing. They searched the Caulobacter genome for distinctive genes or motifs—and got nothing. They looked for Caulobacter proteins or other small molecules contaminating their DNA—and got nothing. There is something yet to be found about Caulobacter DNA that does this.

There is something interesting in the fact that this signal that says “Warning! Go Away!” comes from dead cells.

We could look upon this as being a perfectly sensible system for free-swimming cells to avoid settling down where conditions are bad. The presence of loose Caulobacter DNA is a sure sign that Caulobacter cells have been there, and died. So, from the swimming cell’s point of view, it is not the place to settle down.

However, there is a growing number of researchers who look upon Bacteria as being social organisms—organisms that will not just communicate with each other, but also lay down their lives for others of the same species. So, these researchers say, look at it from the point of view of the stalked cell in the biofilm. You’re producing swimmer cells, each of which has 100% of your DNA. If conditions are bad, it would be worth your life to urge your offspring to get away. From this point of view, cells can actually commit suicide just to send that message.

This debate is as yet unresolved, and this recent finding about glue and antiglue doesn’t answer it one way or the other. However, it makes the amazing glue of Caulobacter seem even more amazing, and forces us to re-write the advertising copy: “Sticks like crazy to EVERYTHING!!!*”

(*except certain DNA sequences. We don’t know why.)

Berne, Cecile, David T. Kysela, and Yves V. Brun (2010). A Bacterial Extracellular DNA Inhibits Settling of Microbial Progeny Cells Within a Biofilm. Molecular Microbiology 77(4), 815-829.

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