Scientists image structure of bacterium protein coat

Not always pathogenic

Bacteria are omnipresent - in the water, the air and the soil, as well as in plants, animals and even people. We tend to think of bacteria as pathogenic, causing disease. We associate them with intestinal upsets and throat infections, pneumonia and blood poisoning. However, the great majority of bacteria are really useful - they play a role in our digestion, clean up waste water in sewage treatment plants, produce yoghurt and cheese from milk, and some are even used in the manufacture of drugs.

All the more reason then for getting to know bacteria really well and finding out how they grow and divide, interact with their surroundings and make us sick, or how we can put their properties to even better use. In spite of centuries of research, however, bacteria still hold many mysteries. A micro-sized mail coat

For fifty years now, bacteriologists have known that most bacteria develop an outside protein layer consisting of thousands of hooked together copies of a single protein.

The structure and function of this so-called S-layer can best be compared to an armor or mail coat. Until now scientists had a very limited understanding of the structure and function of this protective coat, which is rather remarkable, given that some bacteria invest up to a third of their total protein production in its construction.

With the publication of their findings in Nature, VIB researchers Han Remaut and Ekaterina Baranova at the Vrije Universiteit Brussel, together with French and British scientists, have pulled the hitherto unknown S layer out of obscurity. "We succeeded in imaging the structure of the protein coat for one specific bacterium (Geobacillus stearothermophilus) down to its individual atoms," says Han Remaut. "We were also able to determine how the individual proteins attached to each other to form a 2D structure similar to a kind of mail coat from the Middle Ages, but on a molecular scale, of course."

This tour de force required using a combination of technologies, including X-ray equipment and electronic microscopy. The most formidable challenge was converting the proteins into stable crystals. For that part of the research, the scientists used small antibodies, so-called nanobodies. These were able to stabilize the protein crystals so that their structure could be imaged in detail with X-ray diffraction. Protection from the outside world

"What we see confirms our earlier assumption that the S-layer functions as a protective coat against outside threats, such as viruses or proteins targeting the bacterial cell wall," continues Remaut, "because if the same bacteria are grown in a 'friendly' environment, free of extraneous threats, they do not develop an S-layer. We also saw that there are chinks in the armor which allow for the exchange of nutrients and other useful substances with the outside world."

To what extent the protein coat plays a role in disease processes in humans still needs to be determined by the Brussels researchers. The S-layer they imaged was that of a harmless soil bacterium. Some pathogenic bacteria, such as those that cause anthrax (Bacillus anthracis) or the hospital bug Clostridium difficile, also feature this type of armor. "There are indications that these bacteria use their S-layer for attaching to the cells of the host. But whether the S-layer forms a potential starting point for fighting these bacteria is still unclear," adds Remaut. "That will require more research." Interface with nanotechnology

Remaut's research is also being followed with interest by chemists, nanotechnologists and material scientists. The 2D-structure and mechanisms underlying the development of the S-layer makes it suitable as a component or as a model for new nanomaterials. In particular, the self-assembly of the S-layer fascinates scientists. "You can compare this self-assembly to a pile of bricks organizing themselves into a perfectly laid wall, but on a nanoscale - one-billionth the size of a common brick," says Remaut. "Such artificial miniature structures could be used, for example, for efficiently delivering active ingredients, such as drugs, to places in the body that are hard to reach."

This is an excellent example of how fundamental biology research can be a source of inspiration for the development of future nanomaterials.