Assembly of bacterial multi-protein complexes

The type VI secretion system (T6SS) is a multi-subunit machine that is widespread in Gram negative bacteria with an over-representation in Proteobacteria and Bacteroidetes. The T6SS is a contractile machine that uses a spring-like mechanism to propel an effector-loaded needle into the target. The T6SS comprises three sub-complexes: (i) the membrane complex that serves as docking station at the cell envelope and as channel for the passage of the needle during contraction, (ii) the baseplate, which is the assembly platform for (iii) the tail tube/sheath complex.

In the recent years we have focused our efforts on the understanding of the structure and assembly pathway of the membrane and baseplate subcomplexes. We have also identified subunits that coordinate or control tail tube/sheath assembly, termination or contraction. We collaborate with several colleagues in France or abroad, notably the group of R. Fronzes for electron microscopy structural studies.

The type VI secretion system (T6SS) injects toxins to either prokaryotic or eukaryotic cells and is thus directly involved in virulence, and/or participate to clear and colonize niches by killing bacterial competitors. The competitive advantage provided by T6SS on intra and inter-species bacterial interaction in the gut and thus on the composition of the microbiota was recently highlighted. Our goal is to identify and determine the mode of action and the targets of T6SS effector toxins, using pathogenic Escherichia coli and related species as models. We also want to understand how T6SS effectors are loaded on the T6SS machine for delivery and how they are activated in the target cell. Specifically, in the recent years, we characterized an antibacterial phospholipase toxin of enteroaggregative E. coli and its immunity protein Tli1. Three Tle1 toxins interact directly with VgrG, the needle spike of the machine, for delivery in the periplasm of target cells.

The phylum Bacteroidetes is under-studied despite many of its members being important pathogens and commensals. These bacteria distinguish themselves by using the type IX secretion system (T9SS). This machinery is composed of at least 18 proteins assembled to secrete effectors supporting a wide variety of functions.

Notably, in Porphyromonas gingivalis, the main microorganism responsible for periodontitis, the T9SS secretes a cocktail of adhesins and proteases called gingipains to promote tissue invasion.