期刊
PLOS PATHOGENS
卷 10, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1004404
关键词
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资金
- Finnish Academy [273075]
- EACEA
- Wellcome Trust [100280, 079819, 085464]
- Leverhulme Trust [RPG-2012-559]
- US Public Health Service grant [AI-033096]
- Medical Research Council [MR/J006874/1B, G1001664] Funding Source: researchfish
- Wellcome Trust [100280/Z/12/Z] Funding Source: researchfish
- MRC [MR/J006874/1, G1001664] Funding Source: UKRI
- Wellcome Trust [100280/Z/12/Z] Funding Source: Wellcome Trust
- Academy of Finland (AKA) [273075, 273075] Funding Source: Academy of Finland (AKA)
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.
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