Twisting and turning: bacterial flagella
Bacterial cells, such as Escherichia coli (E. coli), use their flagella, hair-like protrusions attached to their cell body, in order to navigate their way through the world. This allows them to avoid harmful environments or to move towards a positive source of nutrition. But how do bacteria control where they want to go? Or is it all down to probability?
Patrick - So the point of this study, we were interested in how the number of flagella on an E. coli cell affects its behaviour. So, E. coli are these single-celled organisms, small bacteria, that have flagella that help them to swim. The flagella basically look like corkscrews that rotate. They can rotate either clockwise or counterclockwise and they switch direction as the cell is swimming. And so, the direction of rotation of the flagella affects how the cell moves. And the cell, basically when it swims, it has two modes. There's one that we call a 'run' where the cell tries to swim in a straight direction and go forward. Occasionally, it does what we call a tumble. In the second tumbling mode, the cell pauses and sort of spins around and it eventually moves in a new direction.
Chris - So, that must introduce something of a problem for the bacterium to have to overcome because to produce meaningful net movement in one direction when it has variable numbers of these propulsion units which appear to be acting independently in this way. How does it surmount that? How do the bacteria end up producing a purposeful movement in a given direction?
Patrick - So generally, when the E. coli are swimming, all of the flagellum rotate in a counterclockwise direction. When they all rotate counterclockwise, they form a bundle where all of the flagella sort of wrap around each other and act as propeller. This pushes the cells forward. As I mentioned the flagella can switch direction. And so occasionally, one or maybe a few of the flagella will switch direction and rotate clockwise. When this happens, it breaks this bundle and that's when the cell pauses and changes direction. And so, the question we were interested in was, how does the number of flagella actually affect this behaviour because you might expect that a cell with more flagella would have a greater probability of having at least one of these flagella switch direction at any given time. And so, our basic prediction was that, cells with few flagella would only change direction once in a while but not very often. Whereas a cell with many flagella, we expected to change direction much more often.
Chris - And is that what you saw?
Patrick - No. To our surprise, what we saw was that a cell with one or two flagellum actually changed direction at about the same rate as the cell with 5, 6, or 7 flagella. So, this is a big surprise to us and it took us awhile to figure out what was actually going on. To look at this, we used two different strains. So, we used one strain in which the signal inside the cell that controls how frequently it's changing direction is controlled by the cell itself. And then we used the second mutant strain in which that signal was not controlled by the cell, but instead was fixed by a signal that we put into the cell.
Chris - Why should who has control make a difference? Why is that useful to you, being able to compare those two?
Patrick - So, in the strain where the cell controls it, these are the cells that are able to respond to an environment. And so, when a cell is going in a direction that's good, it wants to continue going in that direction. And so, it increases the probability of the flagella rotating counterclockwise. So basically, when a cell is going in a good direction, it tries to keep going in that direction. When the cell realises that it's going in a direction that's harmful or bad for the cell, it increases the probability of changing direction.
Chris - I see. So, this is quite neat. So basically, the bacterium is influencing the probability of any flagellum changing its activity and in this way, it is inducing a net change in direction. But it's not necessarily dictating which flagellum or cluster of flagella will do that.
Patrick - That's exactly correct. Then we looked at a second strain in which the signal is not controlled by the cell, but instead it's fixed in time. And so, the reason that we thought this might be affecting how cells of different number of flagella behave, is because in the strain in which the cell controls the signal, at any given time, the signal might be very high or very low. And so, if the signal is high, the probability of all of these flagella switching will be high. And so, many of the flagella can switch potentially at the same time. On the other hand, in the strain where the signal does not change, the probability is constant. And so, there is no compensation for the number of flagella. And basically, what we found was that in the strain where the cell controls the signal, cells with one or two flagella behaved very similar to cells with many flagella. They changed direction at about the same rate.
Chris - So, this is a rather natty and crafty, "clever" way for the bacteria to compensate for the fact they're continuously elaborating new flagella and they may have many, they may have few. But this means, the net result each time, regardless of number, is always going to be the same. It's going to be a purpose for swimming towards or away from an appropriate target.
Patrick - Yeah, that's correct. So, we have to refer to this type of feature as being robust because cells, regardless of how many flagella they have, behave similarly. Like you said, they develop this relatively clever system for compensating for that fact.