Molecular analysis of the Type 9 Secretion System (360G-Wellcome-317933_Z_24_Z)

Bacteria from the phylum Bacteroidota (formerly Bacteroidetes) play an important part in human health. As dominant gut and oral commensals they play a critical role in maintaining a healthy microbiota. They also include the major pathogens responsible for anaerobic infections and severe dental disease. Nevertheless, our understanding of the biology of these organisms is poor. In this proposal we seek a molecular-level understanding of the Type 9 Secretion System (T9SS), a recently-discovered, Bacteroidota-specific, virulence determinant. The T9SS is the most complex protein export system known. Our aim is to understand how this supramolecular machine works. We will use a combination of biochemical, structural, and fluorescence imaging methods to determine how the machine is organised and what the different parts do. We will elucidate how energy is transduced from the inner membrane to the transporter in the outer membrane drawing on recently-realised commonalities in energy transfer between the T9SS and the apparatus involved in Bacteroidota gliding motility.