Biology of infection: A bacterial ballistic system

Bacteria secrete a broad range of specific proteins that can affect the behavior or survival of cells in their environment. Among the specialized transport systems responsible for the export of such factors are so-called Type VI secretion systems.

In collaboration with Axel Mogk of the Center for Molecular Biology Heidelberg (ZMBH), biochemist Petra Wendler at the LMU's Gene Center has now determined the three-dimensional structure of one of these export complexes. "Bacterial species employ these systems primarily to secrete specific toxic proteins directed against competitors or host cells. The protein complexes involved in secretion essentially function as nanosyringes," says Wendler.

Type VI secretion systems were discovered only a few years ago, but they are synthesized by many bacterial species, including important pathogens, such as Vibrio cholerae, the bacterium that causes cholera, and Pseudomonas aeruginosa which can induce severe lung damage during chronic infections.

While antibiotic resistance continues to rise, there is a pressing need for alternative ways to combat bacterial pathogens. In this context, Type VI secretion systems offer an interesting target, as blocking their function would effectively disarm pathogenic bacteria in a highly specific manner.

"However, in order to identify weak points in this bacterial secretion system, we need to obtain further insights into how its export machinery works," says Wendler. "We were able to determine the structure of the contracted form of the outer sheath complex at sub-nanometer resolution. It turns out that its basic architecture and the structural elements that stabilize the complex are related to those of certain proteins found in bacterial viruses, but have been modified in the course of evolution to enable them to serve a secretory function."