The invasion strategy of bacteria
The molecules responsible for this coup are called adhesins. Research has recently uncovered a new family, the trimeric autotransporter adhesins (TAAs), in gram-negative bacteria. This group of bacteria includes many pathogens including Escherichia coli and other gut-inhabiting microbes. The molecular organisation of TAAs follows some surprisingly simple basic building rules. They have a head and a stalk made of building blocks that can be varied and repeated, probably evolved to confer a specific fit with the host. The aim of the recently completed European 'Trimeric Bacterial Autotransporters' (Trimbat) project was to investigate the structure and biochemistry of the TAA family. As the formation of a secure landing and adhesion platform is key to a successful invasion, intricate knowledge of their initiation and building structure would be important for drugs and vaccines to stem infection. The Trimbat team first selected a base containing the YadA protein, and four different stalk lengths. In line with the modular nature of the invasion platform, they then chose a variety of heads including the so-called Cherry-tag and maltose-binding protein (MBP). The researchers successfully designed and expressed hybrid TAAs for in vivo studies of the mechanism and structures involved. Also, by engineering MBP, the folding rate of the protein was slowed down, rendering the YadA head domain larger than normal in the bacteria's extracellular space, which made study of its structure easier. Once the structure of TAAs is fully understood, the next step is to design drugs and vaccines that have the configuration to prevent adhesion to the host and therefore stop the first steps of colonisation. The alternative is to use engineered super-adhesives where needed, perhaps to anchor beneficial bacteria.
