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Bacteria don't have to be icky
Feb 7, 2010, 10:30a - Science

(This is the second in a 3-post series on biology. The first post gave background on the various levels at which biologists analyze organisms. This post discusses bacteria and an interesting behavior that they have called chemotaxis. The last post will present a web app that's an interactive simulator of this behavior. And don't forget the bonus video post. Yes, I had originally thought this would all fit into 2 posts, but sometimes the chunkier the better.)

Alright, now on to the meat of things. I'm going to try to explain what I understand about bacterial chemotaxis as clearly as possible, so that it's accessible to anyone who's finished high school. I must prepare you, though, that it may get somewhat technical. Feel free to ask any questions in the comments, or to shoot me an email.

Bacteria are microscopic, single-cell organisms that are considered to be the most simple form of independent life. "Simplicity", as used here, just refers to the fact that a bacterium is small and so has fewer parts compared to any other independent organism. (As an aside, viruses are even simpler [fewer parts], but since they rely on other organisms to reproduce, they can't be counted in the "independent" category.) The species of bacteria that I'll be focusing on in this post is Escherichia coli. Yes, this very same species of bacteria lives in your gut and helps with your digestion, and some strains are known to make people nastily sick. The strains in which chemotaxis have been studied are non-infectious, though.



Artist's rendition of an individual E. coli. The capsule-shaped object is the single cell (~3 microns [millionths of a meter] in length), and the hair-like tendrils are the flagella, which a bacterium uses as propellers to move around.


So what exactly is chemotaxis? Chemotaxis is an organism's ability to move toward certain chemicals, such as sugar. A bacterium is able to move because it has flagella, which are wispy hairs that can spin like a propeller to propel a bacterium in different directions. When flagella spin in one direction (e.g. clockwise), the bacterium moves ahead, but when flagella spin in the other direction (e.g. counter-clockwise), the flagella get all tangled up, making the bacterium spin around like a bottle. Below is a video of E. coli swimming around (flagella are really tiny so you can't seem them at this resolution):

           

E. coli swimming around. Note that no chemotaxis is occuring in this video, as the bacteria just appear to be swimming in all different directions. (I wanted to show a video of actual chemotaxis, but I wasn't able to find one online.)


As you can see by watching the video, bacteria seem to move smoothly along curved lines, almost forming circles. Occassionally, they slow down, twitch a bit, and then start moving in a new direction. Sometimes they collide with the non-moving bacteria, which I'm assuming either got stuck to the glass slide or are dead.

What people have learned by analyzing bacterial motility (movement) is that they seem to move in a way that's called a "biased random walk". When there's no attractant (sugar) lying around, bacteria just wander, covering the space with no preference for any specific location. They move along their curved paths (called "runs"), and every once in a while, they spin around (called "tumbles") and start on in a new random direction. This is the "random walk" part of the "biased random walk".

The "bias" comes in when there is some sugar lying around, and bacteria want to get to it. If you think about it, there are many strategies you can use to get to something you want. Humans have the ability to see (unlike bacteria), so if there's some chocolate lying on the kitchen counter, we just find it with our eyes and home right in. If we were blind, we might just constantly reach our hands out, feeling around the counter until we touched the chocolate. In a way, bacteria are like blind people. They don't have hands, but they do have tiny receptors on their "skin" (cell membrane) that can bind and sense sugar. Whenever there's sugar around, the sugar changes the probability of whether a bacterium is going to tumble or not. One way to think about it is that as the amount of sugar around a bacterium increases, it tumbles less, because it doesn't want to screw up the fact that life's getting better. But when the sugar starts to decrease, a bacterium "realizes" that it'd rather be back there where there's more sugar, and it tumbles more. Note that they don't seem to be able to choose which new direction they will take - they just spin around randomly and then start swimming again. They keep doing this until the sugar concentration starts increasing again. This concentration-dependent tumble probability introduces a "bias" into a bacterium's normal "random walk", such that it now spends more time at higher sugar concentrations, exhibiting a place preference it didn't show before.

Now, because bacteria are relatively "simple" and genetically tractable (I may write up a separate post to explain what this means - it's too much to go into now), it was somewhat straightforward for researchers to dissect the behavior of chemotaxis into it's molecular parts. I've already mentioned 2 important molecules. First, there are the chemoreceptors that actually sense sugar, which are called methyl-accepting chemotaxis proteins (MCPs). And second, there are the proteins that the flagella are made out of, called flagellin. By a combination of genetic and biochemical analysis, researchers have been able to find the molecules that connect the sensory input with the motor output. I won't go into them in too much detail, but here's a diagram of the molecules involved (circa 2004):

                                             

Molecules involved in bacterial chemotaxis. You can see the sugar-sensors at the top (MCPs), and the flagella at the bottom (the curvy blue thing). In between you can see the proteins CheW, CheA, CheZ, CheY, and CheB, which are important for communicating the external sugar concentration to the flagella.


The bottom-line is this: Researchers have been able to bridge the extremes of biological analysis, connecting the big, obvious changes in behavior with the tiny, hard-to-see changes in molecules. Now that's what biology is all about! Why do we do the things that we do? Because our molecules do the things that they do!

So this is what I knew of bacterial chemotaxis way back in October 2008. But then I wondered if what we thought to be true was actually true. How do we know that the diagram above is right? How do we know that all these molecules are sufficient to create what we actually observe bacteria doing in the real world? In my opinion, the best test of understanding is creation - if you can build from scratch that which you've observed, then that can be damn good evidence that you truly understand what's happening. Though I'm no biochemist, I am an engineer, so I decided to make a computer simulation of what I understood to be happening during bacterial chemotaxis. Instead of diving to the lowest level and simulating the molecules involved, I started out at an intermediate level, just simulating tumble probability directly as function of sugar concentration. And as it turned out, I saw something that I didn't expect, something which surprised me and which I'll share in the next and final blog post in this series.

Below is a teaser of sorts, a static, low-res screenshot of the simulator. The real-deal to follow...

             

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Credits and reference:
- Drawing of single E. coli found online at asymptotia.com/2008/08/11/ecoli-stories/
- Video of E. coli swimming around comes from a lab at the Rowland Institute at Harvard: www.rowland.harvard.edu/labs/bacteria/movies_ecoli.html
- Diagram of molecules involved in chemotaxis came from a paper: Wadhams & Armitage 2004, "Making sense of it all: Bacterial chemotaxis", Nature Reviews Molecular Cell Biology (PDF)

Read comments (2) - Comment

Ruggero - Feb 18, 2010, 1:21a
I suppose that tumble probability increases with sugar concentration, so the bacteria spend more time in the area they like most.


nikhil - Apr 12, 2010, 5:44p
That's an interesting idea which I haven't tried, but the conventional wisdom is actually the opposite. Based on what I've read, it seems that real bacteria actually tumble less when they're moving up a sugar gradient, and tumble more when they're moving down a sugar gradient, though they do adapt and return to a baseline tumbling rate.

It would be interesting to try your idea in the simulator (which I just posted) and see what happens. Unfortunately, there's no easy way to do this in the interface provided, so you'd have to change the javascript to try it out.


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