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Structure and host-receptor recognition studies of Gram-negative bacterial fimbriae assembled via the chaperone/usher pathway

Roy, Saumendra Prasad (2015). Structure and host-receptor recognition studies of Gram-negative bacterial fimbriae assembled via the chaperone/usher pathway. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2015:99
ISBN 978-91-576-8396-0
eISBN 978-91-576-8397-7
[Doctoral thesis]

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Abstract

Enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC), and Yersinia enterocolitica (YE) are the principle etiological agents of acute and persistent diarrhea worldwide including resource-poor and industrialized regions. Adhesion of these pathogens to host receptor is the first important step to deliver toxins and virulent factors to initiate pathogenicity. Coli surface antigen (CS6) of ETEC, aggregative adherence factor-1 (AAF-1) of EAEC, and mucoid Yersinia fimbriae (Myf) of YE are the widely expressed colonization factors (fimbriae or pili) that mediate bacterial adhesion to the small intestinal epithelium. CS6 consists of CssA and CssB, AAF-1 consists of AggA and AggB, and Myf is made of MyfA, which are secreted and assembled on the cell surface via the chaperone/usher pathway. Using X-ray crystallography, we present atomic resolution insight into the fibre forming subunits and show that subunits of these organelles are assembled into a linear polymer by donor strand complementation. Myf is a homo-polymer, AAF-1 is a polymer of AggA subunits decorated by a single copy of the AggB subunit at the tip of the fiber, and CS6 is hetero-polymer of CssA and CssB subunits that are assembled alternately into a single fiber. Using spectroscopic and biochemical studies, we demonstrate that all subunits of these three fimbriae bind to receptors on intestinal epithelial cells, establishing multipoint attachment. The crystal structure of a MyfA-galactose complex reveals the receptor binding site and responsible residues. Structure guided mutagenesis of AggA shows that it binds to fibronectin via a novel electrostatic binding mechanism. Based on our structural and biochemical studies we conclude that CS6, AAF-1, and Myf are adhesive fimbriae of a novel type: they can act as poly-adhesins with rich binding properties. These findings steer the research field forward by revealing insight into receptor-fimbria interactions. This opens a window to search for receptor inhibitor molecules to decrease the infantile death rate and associated malnutrition.

Authors/Creators:Roy, Saumendra Prasad
Title:Structure and host-receptor recognition studies of Gram-negative bacterial fimbriae assembled via the chaperone/usher pathway
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :November 2015
Depositing date:3 November 2015
Volume:2015:99
Number of Pages:59
Papers/manuscripts:
NumberReferences
IRoy SP*, Rahman MM, Yu XD*, Tuittila M*, Knight SD, Zavialov AV (2012). Crystal structure of enterotoxigenic Escherichia coli colonization factor CS6 reveals a novel type of functional assembly. Mol Microbiol. 86(5): 1100-15. doi: 10.1111/mmi.12044. Epub 2012 Oct 10.
IIBerry AA, Yang Y, Pakharukova N, Garnett JA, Lee WC, Cota E, Marchant J, Roy S, Tuittila M, Liu B, Inman KG, Ruiz-Perez F, Mandomando I, Nataro JP, Zavialov AV, Matthews S (2014). Structural insight into host recognition by aggregative adherence fimbriae of enteroaggregative Escherichia coli. PLoS Pathog. 18; 10(9): e1004404. Doi: 10.1371/journal.ppat.1004404. eCollection 2014.
IIISaumendra Roy, Jerry Ståhlberg, Torleif Härd, and Anton V. Zavialov. Myf antigen of Yersinia enterocolitica recognizes host receptor through galactosyl residue in lycosphingolipid. (manuscript).
Place of Publication:Uppsala
Publisher:Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8396-0
ISBN for electronic version:978-91-576-8397-7
ISSN:1652-6880
Language:English
Additional Information:Errata: On page number 7: It should be Roy SP*, Rahman MM*, Yu XD*, Tuittila M*, Knight SD, Zavialov AV (2012). Crystal structure of enterotoxigenic Escherichia coli colonization factor CS6 reveals a novel type of functional assembly. Mol Microbiol. 86(5): 1100-15. doi: 10.1111/mmi.12044. Epub 2012 Oct 10.
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X30 Life sciences
Subjects:Obsolete subject words > NATURAL SCIENCES > Chemistry > Biochemistry
Obsolete subject words > NATURAL SCIENCES > Chemistry > Biochemistry > Molecular biology
Obsolete subject words > NATURAL SCIENCES > Chemistry > Biochemistry > Structural biology
Agrovoc terms:gram negative bacteria, receptors, bacterial antigens, escherichia coli, diarrhoea, x-ray spectroscopy
Keywords:Gram-negative Bacteria, Fimbriae, Structure, Receptor, Binding, X-ray crystallography
URN:NBN:urn:nbn:se:slu:epsilon-e-3045
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3045
ID Code:12776
Faculty:NL - Faculty of Natural Resources and Agricultural Sciences (until 2013)
Department:(NL, NJ) > Department of Chemistry and Biotechnology (140101-161231)
Deposited By: Mr Saumendra Prasad Roy
Deposited On:04 Nov 2015 09:14
Metadata Last Modified:16 Dec 2015 12:24

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