Activation and regulation of the T3SS during infection
Bacteria need to make sure that the right amount of the correct effector proteins is translocated into a target cell without alerting the host immune system. Therefore, substrate specificity and translocation rate of the injectisome must be tightly controlled, in acute as well as in persistent infections.
The activity of the T3SS thus needs to be regulated; however, little is known about how environmental signals regulate the function of the T3SS. Our lab has recently discovered that T3SS composition and function quickly and strongly respond to changes in the external conditions, which provides a striking example for the functional regulation of the T3SS by the environment. We now want to identify the regulatory pathways involved in this regulation, and especially the events at the injectisome itself.
To better understand how different bacteria use the T3SS, we compare its function and regulation in Yersinia enterocolitica and Pseudomonas aeruginosa. Applying our experience in live microscopy to the P. aeruginosa T3SS allows us to build on the wealth of studies that have described its regulatory networks, and to determine the link between the signaling pathways and the T3SS. Regulation of the T3SS in P. aeruginosa is directly relevant for the outcome of nosocomial infections, and hence a better understanding is a key step towards preventing healthcare-related infections. Comparing the regulation of the Y. enterocolitica and P. aeruginosa T3SS, we can discern general and species-specific mechanisms in the regulation of type III secretion, a crucial prerequisite for the development of generic T3SS inhibitors.