Regulatory and binding specificity features of Escherichia coli Ucl fimbriae

Extra-intestinal pathogenic Escherichia coli (ExPEC) are members of a critical priority group of antibiotic resistant pathogens that cause severe human disease. ExPEC produce multiple virulence factors that contribute to host colonisation and infection, including adhesins from the chaperone-usher fimbriae class. ExPEC Ucl fimbriae mediate attachment to human exfoliated uroepithelial cells, biofilm formation and intestinal colonization. Here, we show that the ucl fimbrial genes are predominantly found in ExPEC strains from the B2 phylogeny. Genome editing of representative strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter region that increases Ucl fimbrial expression via activation by the global regulator OxyR, leading to enhanced colonisation of the mouse gut. We determined the glycan receptor repertoire and crystal structure of the UclD lectin domain, as well as the homologous UcaD fimbrial adhesin from Proteus mirabilis. Despite their conserved tertiary structure, glycan array analysis showed both adhesins recognise different oligosaccharides. Structural analyses of UcaD in complex with monosaccharides revealed a glycan binding pocket, providing a framework for the development of novel anti-adhesion drugs