Periodic Reporting for period 3 - AimingT6SS (Mechanisms of dynamic localization of the bacterial Type 6 secretion system assembly)
Reporting period: 2024-01-01 to 2025-06-30
Bacterial cells require mechanisms to deliver proteins and toxins synthesized in their cytosol to the environment or into the host cells during infection. One of the mechanisms that evolved is the so-called Type VI secretion system. This system works similarly to the bacteriophage contractile tails and can be imagined as a bacterial nano-speargun. While the structure and the assembly of this secretion was described in detail in the past, we currently lack understanding of its intricate regulation. It is known that some bacteria, including human pathogens, can react to contact with neighboring cells and within seconds assemble the secretion system to deliver a cocktail of toxins into target cells. In this grant, we study the molecular mechanisms behind this regulation. Our work will provide novel insights into the components of bacterial signaling cascades in multiple human pathogens. In addition, we will unravel the role of this secretion system during bacterial interactions as well as during infection. This work will advance our understanding of how bacterial cells interact with their environment and thus open new possibilities for intervention.
During this project we have identified novel pathway that allows Acinetobacter and Burkholderia to precisely localize the Type VI secretion system to the site of contact with neighboring bacterial cells to increase the efficiency of delivery of anti-bacterial toxins. We have further obtained novel insights into the regulation of the secretion system assembly during spread of intracellular pathogens within and between host cells.
Our data significantly improved our understanding of the Type VI secretion system assembly by providing new visualization and characterization of the assembly process in the context of bacterial cell-cell interaction as well as bacterial infection. We expect to provide detailed description of the underlying molecular mechanisms and thus initiation of novel lines of research into the fundamental principles of signal transduction in bacteria as well as understanding of the assembly of complex nano-machines.