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

Autor: Andrea A Berry, Yi Yang, Natalia Pakharukova, James A Garnett, Wei-chao Lee, Ernesto Cota, Jan Marchant, Saumendra Roy, Minna Tuittila, Bing Liu, Keith G Inman, Fernando Ruiz-Perez, Inacio Mandomando, James P Nataro, Anton V Zavialov, Steve Matthews
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS Pathogens, Vol 10, Iss 9, p e1004404 (2014)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1004404
Popis: 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.
Databáze: Directory of Open Access Journals
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