Max Planck: Structure of bacterial virulence channel elucidated

Research lead

Scientists from the Max Planck Institute for Infection Biology in Berlin, the Max Planck Institute for Biophysical Chemistry in Göttingen, and the Federal Institute for Materials Research and Testing, have succeeded in elucidating the basic principles of the assembly of the transport channel which bacteria use to deliver virulence factors and infect their hosts.

They say this is an important starting point for the development of new drugs that might interfere considerably earlier than antibiotics in the course of infection.

Every day the human organism is confronted with a huge variety of pathogens, most of which are fended off by the immune system. To execute a successful infection, bacteria must therefore manipulate the host and secrete virulence factors through a transport channel located in the bacterial membrane.

Some bacteria, such those which cause dysentery, food poisoning and typhoid fever, have developed a specialised transport mechanism called the Type three secretion system. This structure resembles a syringe with the base embedded in the bacterial membrane and the needle protrudes out of the bacteria. Bacteria use this to inject virulence factors directly into the host cell.

To date, little was known about how bacteria build this nano-syringe. The scientists say they have now succeeded in elucidating the fundamental principles of how it is assembled. First the bacterium synthesises the proteins in the cell interior, transports them through the syringe to the outside, and stacks them one after the other onto the tip of the growing needle. The scientists also showed that the proteins change their three-dimensional structure during the assembly process, pinpointing the exact structural changes down to the single amino acid level.

These results open new perspectives for the development of anti-infectives that inhibit the assembly of the needle and the injection of virulence factors into the host cell. This would be a major advantage over antibiotics, which have to travel through the membrane into the bacteria to be able to kill it.