title: Structural basis for adaptation of lactobacilli to gastrointestinal mucus.
abstract: The mucus layer covering the gastrointestinal (GI) epithelium is critical in selecting and maintaining homeostatic interactions with our gut bacteria. However, the underpinning mechanisms of these interactions are not understood. Here, we provide structural and functional insights into the canonical mucus-binding protein (MUB), a multi-repeat cell-surface adhesin found in Lactobacillus inhabitants of the GI tract. X-ray crystallography together with small-angle X-ray scattering demonstrated a 'beads on a string' arrangement of repeats, generating 174 nm long protein fibrils, as shown by atomic force microscopy. Each repeat consists of tandemly arranged Ig- and mucin-binding protein (MucBP) modules. The binding of full-length MUB was confined to mucus via multiple interactions involving terminal sialylated mucin glycans. While individual MUB domains showed structural similarity to fimbrial proteins from Gram-positive pathogens, the particular organization of MUB provides a structural explanation for the mechanisms in which lactobacilli have adapted to their host niche by maximizing interactions with the mucus receptors, potentiating the retention of bacteria within the mucus layer. Together, this study reveals functional and structural features which may affect tropism of microbes across mucus and along the GI tract, providing unique insights into the mechanisms adopted by commensals and probiotics to adapt to the mucosal environment.
authors.affiliation: Institute of Food Research, Gut Health and Food Safety Institute Strategic Programme, Norwich Research Park, Norwich, NR4 7UA, UK.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Etzold
authors.forename: Olivia I
authors.initials: OI
authors.lastname: Kober
authors.forename: Donald A
authors.initials: DA
authors.lastname: Mackenzie
authors.forename: Louise E
authors.initials: LE
authors.lastname: Tailford
authors.forename: A Patrick
authors.initials: AP
authors.lastname: Gunning
authors.forename: John
authors.initials: J
authors.lastname: Walshaw
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hemmings
authors.forename: Nathalie
authors.initials: N
authors.lastname: Juge
mesh_terms: D000222:Adaptation, Physiological; D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007778:Lactobacillus / Q000737:chemistry / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000382:microbiology*; D017434:Protein Structure, Tertiary
chemical_list: D018829:Adhesins, Bacterial; D002352:Carrier Proteins; D009077:Mucins