Identification, Architecture, Evolution and Adaptation of a unique T6SS membrane complex in Bacteroidetes – CAMELEON

The Bacteroidetes phylum is a dominant member of the Human gut microbiota, where it has a key role in regulating its composition and maintaining good health. Many of these bacteria harbor a type VI secretion system (T6SSiii) that delivers protein effectors to other bacteria. This allows commensals to outcompete other bacteria, including pathogens. The T6SS resembles a nanoscale harpoon that is rapidly ejected to deliver toxins into prey cells. Proteobacteria’s T6SSi accomplish this feat by passage of the T6SS needle through a membrane complex (MC). A wealth of high-resolution structural information is already available for the T6SSi. Paradoxically, little is known on the widespread Bacteroidetes T6SSiii that dominates the human microbiome. Remarkably, Bacteroidetes T6SSiii lacks homology to the already characterized MC of T6SSi, which means that we ignore many key aspects of its function. We identified 5 novel genes encoding an unique Bacteroidetes T6SSMC. We will leverage bacteriology, structural biology, and bioinformatics to uncover the evolution and the structure of the Bacteroidetes T6SSMC, as well as its molecular adaptation to the rest of the T6SS. Our project’s objectives are: (1) What is the composition and unique architecture of the Bacteroidetes T6SSMC?; (2) How does the Bacteroides-specific MC interact with the otherwise conserved baseplate complex? And (3) how did it emerge and evolve? Our studies and the accompanied structural breakthroughs will facilitate comparison to the Proteobacterial T6SSMC and offer a unique glimpse of deep macromolecular and structural convergent evolution.