Bacteroidotes species represent one of the two dominant Phyla in the human intestinal microbiome. These highly abundant keystone species profoundly impact host health by breaking down complex carbohydrates into host-accessible nutrients, preventing pathogen colonisation, synthesising vitamins and secondary bile acids. Metagenomic sequencing has begun illuminating the broad genetic diversity of this Phyla, yet the function for ∼50% of their genetic content remains functionally uncharacterized.
 
Bacteroides rely on their cell surfaces as critical interfaces for survival, enabling nutrient acquisition, immune evasion, and protection against environmental insults. In the competitive gut environment, surface molecules mediate essential interactions with their host and other microbes. In Gram-negative bacteria, structures like adhesins, pili, flagella, surface layers (S-layer), outer-membrane components of Starch Utilisation Systems (a.k.a. Polysaccharide Utilisation Loci (PULs)), and Type 6 secretion systems (T6SSs) provide strong competitive advantages. Although these structures share the same physical space, how they cluster, organise and synergise remains unknown.
 
Our joint project aims to systematically identify and characterize protein complexes on the cell surface of commensal gut bacteria and build towards an understanding of the machinery responsible for their translocation and assembly at the outer-membrane. By integrating systems-wide analysis with high-resolution in situ structural biology approaches, we seek to uncover mechanisms underlying gut microbiome functionality and identify new opportunities for microbiome-targeted interventions and novel applications.