Structural insight into host recognition by aggregative adherence fimbriae of enteroaggregative Escherichia coli.
e1004404 - ?
MetadataShow full item record
Enteroaggregative Escherichia coli (EAEC) is a leading cause of acute and persistent diarrhea worldwide. A recently emerged Shiga-toxin-producing strain of EAEC resulted in significant mortality and morbidity due to progressive development of hemolytic-uremic syndrome. The attachment of EAEC to the human intestinal mucosa is mediated by aggregative adherence fimbria (AAF). Using X-ray crystallography and NMR structures, we present new atomic resolution insight into the structure of AAF variant I from the strain that caused the deadly outbreak in Germany in 2011, and AAF variant II from archetype strain 042, and propose a mechanism for AAF-mediated adhesion and biofilm formation. Our work shows that major subunits of AAF assemble into linear polymers by donor strand complementation where a single minor subunit is inserted at the tip of the polymer by accepting the donor strand from the terminal major subunit. Whereas the minor subunits of AAF have a distinct conserved structure, AAF major subunits display large structural differences, affecting the overall pilus architecture. These structures suggest a mechanism for AAF-mediated adhesion and biofilm formation. Binding experiments using wild type and mutant subunits (NMR and SPR) and bacteria (ELISA) revealed that despite the structural differences AAF recognize a common receptor, fibronectin, by employing clusters of basic residues at the junction between subunits in the pilus. We show that AAF-fibronectin attachment is based primarily on electrostatic interactions, a mechanism not reported previously for bacterial adhesion to biotic surfaces.
AuthorsBerry, AA; Yang, Y; Pakharukova, N; Garnett, JA; Lee, WC; Cota, E; Marchant, J; Roy, S; Tuittila, M; Liu, B; Inman, KG; Ruiz-Perez, F; Mandomando, I; Nataro, JP; Zavialov, AV; Matthews, S
Showing items related by title, author, creator and subject.
Young, JC; Clements, A; Lang, AE; Garnett, JA; Munera, D; Arbeloa, A; Pearson, J; Hartland, EL; Matthews, SJ; Mousnier, A;... (2014-12)The hallmark of enteropathogenic Escherichia coli (EPEC) infection is the formation of actin-rich pedestal-like structures, which are generated following phosphorylation of the bacterial effector Tir by cellular Src and ...
Purification, crystallization and preliminary X-ray diffraction analysis of the Escherichia coli common pilus chaperone EcpB. Garnett, JA; Diallo, M; Matthews, SJ (2015)Pili are key cell-surface components that allow the attachment of bacteria to both biological and abiotic solid surfaces, whilst also mediating interactions between themselves. In Escherichia coli, the common pilus (Ecp) ...
Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis. Pakharukova, N; Garnett, JA; Tuittila, M; Paavilainen, S; Diallo, M; Xu, Y; Matthews, SJ; Zavialov, AV (2015-11)Gram-negative pathogens express fibrous adhesive organelles that mediate targeting to sites of infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher pathways. ...