Saturday, July 12, 2008

crazy bacteria

Another sample chapter from the "crazy" part of my book The birds, the bees and the platypuses, which is released in the US on July 14.

All together now

I have always enjoyed challenging the traditional view that humans are the “highest” life form on Earth and everything else is more or less primitive. For instance, bacteria aren’t quite as dumb as they may appear. Large numbers of them can coordinate their activities in time and space, relying on a form of chemical communication known as quorum sensing. Social behavior in bacteria? What a crazy idea …

An old but persistent myth has it that our own species Homo sapiens sapiens represents the most sophisticated life form on Earth, while bacteria are the most primitive one. Douglas Adams has famously overturned the first part of this myth, and microbiologists are now beginning to realise that bacteria are a lot more sophisticated than we mere mortals used to think. True, the few species that can be easily cultivated in the lab are often well described by the assumption of a single cell programmed to divide after a certain time as long as there is enough food around. But if you observe bacteria out in the wild, they are a lot more complex and less predictable.

By now, microbiologists estimate that the majority of the bacterial biomass is in fact not found as free-living single cells, but rather involved in some kind of higher organisation, including symbiosis with other organisms (e.g. in lichens or animal guts) and biofilms. Cyanobacteria can become part of lichens which look deceptively like higher plants, and also in layer structures which obey strict structural organization on large scales. Colonies of luminescent bacteria can send out precisely coordinated flashes of light. All these “social” activities require each individual bacterium to know of the presence of the others and to communicate with them. For this purpose, they have a chemical signalling system known as quorum sensing.

It was originally discovered in luminescent bacteria, which only light up when there are many of their friends around. In the 1970s, researchers showed that the bacteria secrete a molecular messenger, called the autoinducer, into the medium, and only produce light when they sense a threshold concentration of this molecule. For many years, biologists believed this communication to be specific to bioluminescence. It was only in the 1990s that quorum sensing turned out to be a much more general phenomenon, involved in disparate processes including synthesis of antibiotics in Erwinia carotovora, and the production of virulence factors in pathogenic bacteria.

The molecular mechanisms of quorum sensing have long remained mysterious. In 2002, two crystal structures of proteins involved in the process allowed researchers to put together at least some of the fundamental pieces of the mechanism. The group of Frederic Hughson at Princeton University (New Jersey) identified a hitherto elusive autoinducer, known as AI-2 by solving the crystal structure of its receptor which turned out to contain the AI-2 molecule. While many of the bacterial pheromones known so far are specific to one species, AI-2 appears to be widely distributed and might even serve as a communication device between different species.

The receptor in question was LuxP, a protein involved in the coordinated bioluminescence of the marine bacterium Vibrio harveyi (a harmless distant relative of the cholera germ, named after the pioneer of bioluminescence research, E.Newton Harvey). While the protein structure as such was similar to those of other binding proteins located in the periplasm (the space between cell membrane and cell wall), it was the unusual chemical structure of the autoinducer trapped inside, representing the first example of a biomolecule containing boron, which secured its place on the pages of Nature.

A few months later, the group of Andrzej Joachimiak at the Argonne National Laboratory (Argonne, Illinois) presented another crystal structure of a key protein involved in quorum sensing. Their target is the protein TraR from the plant pathogen Agrobacterium tumefaciens. This protein is related to another quorum sensor from the bioluminescence system and constitutes a direct link between pheromone recognition and the resulting change in gene expression, as it acts both as a signal receptor and as a transcription enhancer. The Argonne group managed to catch it in flagranti, with two molecules of the autoinducer and a piece of the target DNA bound to the protein dimer.

One of the most intriguing aspects of the resulting structure is that the pheromone appears to be completely encapsulated within the protein fold. In accordance with earlier biochemical work indicating that the protein acquires resistance against protease digestion when binding the small molecule, this finding suggests that the sensor “folds around” its messenger molecule. In other words, it starts out from some more loosely folded, probably monomeric conformation, and only folds into the DNA-binding dimer when it has secured its two molecules of the autoinducer. Thus, binding of the signalling molecule is an essentially irreversible switch from an inactive TraR to the active conformation.

As A.tumefaciens makes its living by invading plants and setting up colonies in structures which look like tumours (hence the name), it is rather important for the individual bacteria to know whether they are part of a successful invasion troop, or whether they are out on their own. The traR gene is switched on as soon as the bacterium senses certain plant-specific chemicals, and the individualist turns into a part of a coordinated army from then on. Deeper understanding of bacterial communication gathered from the present structural work and future research should hopefully enable us also to fight bacterial invasions of our own bodies more efficiently - seeing that we are supposedly smarter than they are.


Further reading

The quorum sensing site:
X. Chen et al., Nature, 2002, 415, 545.
R. Zhang et al., Nature, 2002, 417, 971.

What happened next

No bacterial communications have reached my sensors in recent years, but I am sure that a lot of interesting work continues to be performed in this field – try visiting the quorum sensing site to get an impression of what’s going on.


PS in fact there is something on the social life of bacteria in the current issue of Science magazine, which I haven't read yet, but I may end up writing something about that, too.

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