The pirate in the microbe: Bacteria do not move entirely randomly when they explore the surface of host cells

Biologists have known for some time that the pili adhere to surfaces while the microbes pull themselves along using these, reabsorbing them in order to move. However, some microbes such as Neisseria gonorrhoeae, the pathogen that causes gonorrhoea, extend their pili in all directions. Thus their route also depends on which pilus is currently exerting the strongest pull force. Academics can now explain why the bacteria nevertheless move in a straight line for at least one to two seconds. A more detailed understanding of this mechanism will enhance our comprehension of how bacteria infect cells and may also provide an approach to combating them.

If pirates were to find themselves in a situation in which they could only move in the same way as Neisseria gonorrhoeae, it would be easy to put a stop to their activities as naval vessels would very soon have them surrounded. If they were to go on the attack as the best way of defending themselves, the situation would soon develop into a complete farce. Instead of astutely taking over the fastest ship and using it to flee, the pirates would first engage in a kind of tug-of-war to determine which boat to target with their grappling hooks. At least, this is similar to the way that N. gonorrhoeae apparently moves on the surface of a host cell. By playing tug-of-war with a random outcome, the bacterium 'decides' which direction to take to form a colony with others of its own kind or to find the best access route into the cell. But, as researchers at the Max Planck Institute of Colloids and Interfaces working under Stefan Klumpp and another team headed by Berenike Maier at Cologne University have now found, the microbes do not wander around quite as randomly as might be expected.

The bacteria appear to make greater progress in their exploration of a surface than if their route were to be entirely randomly determined. This helps them scan their environment more rapidly and identify a place where they can enter the host cell or find other bacteria with which they can form a colony.

The one-dimensional tug-of-war model does not explain everything

The biological 'tug-of-war' process is not only used by some bacteria to determine in which direction to move. Cells also use this mechanism to decide where to transport their enzymes and other biomolecules. They also make use of a spindle apparatus along which the chromosomes are distributed when the cells divide, resulting in a kind of intra-cellular sports competition. Usually the tug-of-war that takes place in a cell is all about competition for movement in two opposite directions, something that sports teams have known since ancient times. Biophysicists have already gained a thorough understanding of this process on the one-dimensional level. Yet this does not fully explain how Neisseria gonorrhoeae moves. "Thus far there has only been one model, that of a one-dimensional tug-of-war in cells," explains Stefan Klumpp. "However, if we simply extend this model to two dimensions, the theoretical predictions do not concur with the actual behaviour of the bacteria observed in experiments."

In a one-dimensional tug-of-war, it is chance alone that determines which side will win and in which direction a load should be transported. But applying this principle in two dimensions would mean that N. gonorrhoeae would have to change direction constantly once it has managed to pull itself forward a little along one of its biological grappling hooks and reabsorbed it in the process. "From our experiments, however, it is apparent that the bacterium continues in the same direction for more than one pilus length," says Berenike Maier, who led the experimental part of the study at Cologne University. She and her colleagues placed these single-cell organisms on protein-coated glass plates and watched them creep around. They also observed how the bacteria were able to use their pili to pull tiny balls out of the focus of laser tweezers, something that required a surprising amount of mechanical force.

Mechanical memory of the direction of movement

Stefan Klumpp and his team made use of these experimental results to develop a computer model that realistically depicts the routes taken by the bacteria. "We identified two mechanisms that provide the bacterium with the ability to remember the direction in which it is currently moving," says the academic. "When we take these into account in our model, this closely reproduces the behaviour observed in our experiments."

Working in collaboration with Alexander Schmidt, who conducts research at the Centre for Molecular Biology of Inflammations at Münster University, he found that a bacterium tends to extend bundles of two or three pili in a specific direction. This increases the probability that several successive pili will achieve their goal in the bacterial tug-of-war, pulling the organism in one and the same direction. The chances of this happening are increased because the bacterium manages to extend another pilum with the same orientation in a place where it has just reabsorbed one. This is ensured by a protein complex located in the corresponding position on the cell wall, which continues to assemble a bacterial grappling hook from its components and projects it from the cell in the same direction each time one has just been retracted. "The directional memory of Neisseria gonorrhoeae is therefore based on purely mechanical processes," says Berenike Maier.

Understanding this movement may lead to the development of a therapeutic approach The academics suspect that other bacteria manage to increase the 'length of their stride' in a similar fashion -- at least those with a rather rotund shape, which tend to extend pili in all directions. Long and thin microbes, on the other hand, only extend their means of transport at either end and control the route they take using biochemistry. However, biochemical signals also play a role in the movement of N. gonorrhoeae. "It is probable that biochemical signals transmitted by the host cell cause the bacterium to shorten its stride at a point where infection is possible," adds Stefan Klumpp. Thus the single-cell organisms are less likely to form mini-bundles, thus preventing them from 'overshooting' the access gate to the cell. A better understanding of how infectious microbes move with the aid of their pili could also be of medical significance and could help with the development of new antibiotics. It is only when the pathogens can use their grappling hooks in the usual manner that they manage to enter a host cell.