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Structural insight into host recognition by aggregative adherence fimbriae of enteroaggregative Escherichia coli

DOI: 10.1371/journal.ppat.1004404 DOI Help
PMID: 25232738 PMID Help

Authors: Andrea A. Berry (University of Maryland School of Medicine) , Yi Yang (Imperial College London) , Natalia Pakharukova (University of Turku) , James Garnett (Imperial College London) , Wei-Chao Lee (Imperial College London) , Ernesto Cota (Imperial College London) , Jan Marchant (Imperial College London) , Saumendra Roy (University of Turku) , Minna Tuittila (University of Turku) , Bing Liu (Imperial College London) , Keith G. Inman (Paragon Bioservices) , Fernando Ruiz-Perez (University of Virginia School of Medicine) , Inacio Mandomando (University of Virginia School of Medicine) , James P. Nataro (University of Virginia School of Medicine) , Anton V. Zavialov (University of Turku) , Steve Matthews (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 10 (9)

State: Published (Approved)
Published: September 2014
Diamond Proposal Number(s): 9424

Open Access Open Access

Abstract: 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.

Journal Keywords: Pili and fimbriae; Crystal structure; Bacterial biofilms; NMR spectroscopy; Protein structure; Lysine; Disulfide bonds; Polymers

Diamond Keywords: Bacteria; Gastroenteritis

Subject Areas: Biology and Bio-materials

Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: ID23-1 at ESRF

Added On: 26/03/2015 13:04


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)