Structural Insight into Host Recognition by Aggregative Adherence Fimbriae of Enteroaggregative Escherichia coli

PLoS Pathogens

Andrea A. Berry¹  Ernesto Cota²  Keith G. Inman²  Jan Marchant²  Yi Yang²  James A. Garnett²  Wei-chao Lee²  Minna Tuittila³  Natalia Pakharukova⁴  Bing Liu⁴  Saumendra Roy⁴  Steve Matthews⁴  James P. Nataro⁵  Anton V. Zavialov⁵  Inacio Mandomando⁵  Fernando Ruiz-Perez⁶ 

[1] Center for Vaccine Development, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, United States of America;Centre for Structural Biology, Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom;Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, Uppsala BioCentre, Uppsala, Sweden;Department of Chemistry, University of Turku, Turku, JBL, Arcanum, Turku, Finland;Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America;Paragon Bioservices, Inc, Baltimore, Maryland, United States of America

关键词: Pili;    fimbriae;    Crystal structure;    Protein structure;    Lysine;    NMR spectroscopy;    Bacterial biofilms;    Disulfide bonds;    Biofilms;   

DOI  :  10.1371/journal.ppat.1004404

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY