Bacterial Secretion Systems
Dr. Andreas Diepold
Bacteria that live in contact to eukaryotic cells greatly benefit from being able to manipulate host cell behaviour. One of the most direct and elegant ways to reach this aim is the type III secretion system (T3SS), a molecular syringe also known as “injectisome”, used by gram-negative bacteria to inject effector proteins into host cells.
The T3SS is essential for virulence in many important human pathogens, including Salmonella, Shigella, and pathogenic Escherichia coli, that cause several millions of deaths per year. It is also important in hospital infections, for example by Pseudomonas aeruginosa, where presence of a functional T3SS is associated with higher mortality in animal models and increased antibiotic resistance, severe disease, and a bad prognosis in infected humans.
While the translocated effector proteins vary between different bacterial species, the T3SS itself is highly conserved, which makes it an attractive target for anti-virulence therapeutics. However, although parts of the evocative “injection device” structure of the injectisome have been characterized in great detail (Fig. 1A), we know surprisingly little about the molecular function of the T3SS. How do the components of the injectisome interact to allow the fast and ordered translocation of the effectors? Which molecular events lead to effector export? And how does the injectisome respond to external signals?
My group wants to understand how the T3SS works on the molecular level, how it is activated and regulated during the infection process, and how we can control or inhibit its function.
To this aim, we analyze the T3SS in live bacteria, both under controlled conditions, and in contact to host cells. We apply cutting edge live-cell and superresolution microscopy, complemented by a various biochemical and genetic methods, and closely collaborate with leading researchers within and beyond the Max Planck Institute.