The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease

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Madar Johansson , M , Belurier , E , Papageorgiou , A C , Sundin , A P , Rahkila , J , Kallonen , T , Nilsson , U J , Maatsola , S , Nyholm , T K M , Kapyla , J , Corander , J , Leino , R , Finne , J , Teneberg , S & Haataja , S 2020 , ' The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease ' , Journal of Biological Chemistry , vol. 295 , no. 42 , pp. 14305-14324 . https://doi.org/10.1074/jbc.RA120.014818

Title: The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease
Author: Madar Johansson, Miralda; Belurier, Eva; Papageorgiou, Anastassios C.; Sundin, Anders P.; Rahkila, Jani; Kallonen, Teemu; Nilsson, Ulf J.; Maatsola, Santeri; Nyholm, Thomas K. M.; Kapyla, Jarmo; Corander, Jukka; Leino, Reko; Finne, Jukka; Teneberg, Susann; Haataja, Sauli
Contributor: University of Helsinki, Department of Mathematics and Statistics
University of Helsinki, Biochemistry and Biotechnology
University of Helsinki, University of Turku
Date: 2020-10-16
Language: eng
Number of pages: 20
Belongs to series: Journal of Biological Chemistry
ISSN: 0021-9258
URI: http://hdl.handle.net/10138/324850
Abstract: Streptococcus suis is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, S. suis is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic S. suis are limited, new therapeutic approaches are needed. The virulence factor S. suis adhesin P (SadP) recognizes the galabiose Gal alpha 1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes P-N and P-O. We show here that subtype P-N is distributed in the systemic strains causing meningitis, whereas type P-O is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype P-N strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type P-N SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type P-O SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type P-N SadP binding to Gb4 could be used to selectively target S. suis in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.
Subject: glycolipid
adhesin
cell surface receptor
ligand-binding protein
glycobiology
globotetraosylceramide
globotriaosylceramide
Gb3
Gb4
SadP
BACTERIAL ADHESION
MASS-SPECTROMETRY
PROTEIN
GLYCOLIPIDS
GLYCANS
IONS
COLI
SADP
1182 Biochemistry, cell and molecular biology
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