To compete over resources, bacteria use various secretion systems to deliver enzymes and toxins to neighboring cells or their environment. The type VI secretion system (T6SS) is a dynamic assembly found in many gram-negative bacteria including human pathogens. T6SS can physically push toxins across membranes of bacterial and eukaryotic cells. Recent progress in structural biology and live-cell imaging has provided insights into the assembly and function of T6SS in many different species. However, the spatio-temporal regulation of T6SS assembly remains poorly understood. As an example of spatial regulation, I will present our recent work that showed that T6SS assembly is accurately localized to the site of cell-cell contact in two different human pathogens. This regulation involves a class of periplasmic proteins and an outer membrane porin. I will also discuss how bacteria can detect outer-membrane damage and quickly localize assembly of their T6SS to retaliate to attacks from other bacteria. As an example of temporal regulation, I will show how an intracellular human pathogen uses one of its five T6SSs to induce cell-cell fusions and spread within the host. I will show that while the T6SS is expressed in all intracellular bacteria it is predominantly assembled in short bursts in bacteria localized near membranes or in membrane protrusions while the bacteria are moving from cell to cell using actin tails. I will further show that the pathogen efficiently disrupts host cell membranes and spreads without alerting cellular responses such as recruitment of galectin-3. Taken together, I will provide new insights into the mechanisms underlying spatiotemporal regulation of T6SS assembly and its role in interbacterial competition and pathogenesis.
Link to a recent review: