AVZ is supported by the Finnish Academy (grant 273075; http://sciencenordic.com/partner/academy-finland). The EACEA (http://eacea.ec.europa.eu) supports NP for an Erasmus Mundus scholarship. SM is supported by the Wellcome Trust (Senior Investigator Award 100280, Programme grant 079819; equipment grant 085464; http://www.wellcome.ac.uk)) and the Leverhulme Trust (RPG-2012-559; http://www.leverhulme.ac.uk). JPN and AAB are supported by a US Public Health Service grant (AI-033096; www.usphs.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Berry, AA

Cota, E

Garnett, JA

Inman, KG

Lee, W-C

Liu, B

Mandomando, I

Marchant, J

Matthews, S

Nataro, JP

Pakharukova, N

Roy, S

Ruiz-Perez, F

Tuittila, M

Yang, Y

Zavialov, AV

PLoS Pathogens

PubMed

Berry Andrea A.

Yang Yi

Pakharukova Natalia

Garnett James A.

Lee Wei-chao

Cota Ernesto

Marchant Jan

Roy Saumendra

Tuittila Minna

Liu Bing

Inman Keith G.

Ruiz-Perez Fernando

Mandomando Inacio

Nataro James P.

Zavialov Anton V.

Matthews Steve

Public Library of Science (PLOS)

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

Crossref

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

<div><p>Enteroaggregative <i>Escherichia coli</i> (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.</p></div

Andrea A. Berry (565386)

Yi Yang (116183)

Natalia Pakharukova (631544)

James A. Garnett (631545)

Wei-chao Lee (631546)

Ernesto Cota (631547)

Jan Marchant (472714)

Saumendra Roy (631548)

Minna Tuittila (631549)

Bing Liu (70818)

Keith G. Inman (631550)

Fernando Ruiz-Perez (569536)

Inacio Mandomando (2806633)

James P. Nataro (252024)

Anton V. Zavialov (631551)

Steve Matthews (631552)

The Francis Crick Institute

Structural Insight into Host Recognition by Aggregative Adherence Fimbriae of Enteroaggregative <i>Escherichia coli</i>

Queen Mary Research Online

Spiral - Imperial College Digital Repository

English

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

Andrea A Berry

James A Garnett

Keith G Inman

James P Nataro

Anton V Zavialov

Directory of Open Access Journals

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

file:///data/core-remote/dit/data/public_library_of_science/pdf/380/ZnRwOi8vZnRwLm5jYmkubmxtLm5paC5nb3YvcHViL3BtYy9vYV9wYWNrYWdlLzViLzJhL1BNQzQxNjk1MDcudGFyLmd6.pdf

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

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Public Library of Science (PLOS)

Crossref

Public Library of Science (PLOS)

The Francis Crick Institute

Queen Mary Research Online

Spiral - Imperial College Digital Repository

Directory of Open Access Journals