Research of the Microbial Receptors Section focuses on the cell surface components of oral streptococci and actinomyces that mediate dental plaque formation leading to the initiation of inflammation at surrounding sites. These components include coaggregation receptor polysaccharides (RPS) that promote interbacterial adhesion between members of the dental plaque biofilm community. We previously showed that adhesin-mediated recognition of RPS depends on the presence of host-like motifs (i.e. GalNAc1-3Gal or Gal1-3GalNAc) in the repeating oligosaccharide subunits of these linear polysaccharides. From comparative molecular, structural and functional studies of ribitol-5-phosphate-containing types of RPS produced by Streptococcus oralis and closely related serogroup 10 capsular polysaccharides of S. pneumoniae, we have now shown that recognition of these motifs also depends on an adjacent structural feature (i.e. 1-6 linked Galf) present in all known types of RPS. These findings suggest a common design for polysaccharides that function as recognition molecules for interbacterial adhesion and thereby provide a structural paradigm for studies of dental plaque biofilm development. In studies of other bacterial surface components that mediate colonization and dental plaque formation, we associated the well-established adhesive properties of Actinomyces oris type 1 and type 2 fimbriae with specific tip or shaft fimbrillins. Binding of type 1 fimbriae to salivary proline-rich proteins that coat the tooth surface was shown to depend on tip fimbrillin FimQ rather than shaft fimbrillin FimP, whereas binding of type 2 fimbriae to RPS-bearing streptococci and host cells was mediated by shaft fimbrillin FimA rather than tip fimbrillin FimB. The identification of specific adhesins opens new approaches for identifying and defining type 1 and type 2 fimbriae-mediated interactions that are critical for initial colonization and biofilm development. Like the fimbrial adhesins of A. oris, the sialic acid-binding adhesin (Hsa) of S. gordonii DL1 contributes to oral colonization. Importantly, Hsa is also a virulence determinant in pathogenesis of experimental infective endocarditis. We have now found that the strength of Hsa-mediated bacterial adhesion increases with increasing shear force (i.e. flow across a surface). This property of Hsa has important implications for understanding adhesion of oral streptococci in turbulent environments such as in the endocardium. In addition to interbacterial adhesion, the ability of different species to utilize salivary proteins and glycoproteins as substrates for growth is essential for survival of the dental plaque biofilm community. We hypothesize that cross-feeding between species is a major driving force for biofilm development and that the spatial arrangement of different cell types within biofilm communities facilitates cooperative enzymatic attack and utilization of salivary substrates by these bacteria. We recently found that growth of A. oris in whole saliva is greatly enhanced in co-cultures with coaggregating S. oralis and are currently comparing cell surface glycoside hydrolase activities of these species using methylumbelliferone-sugar and glycoprotein substrates. We are also preparing deletion mutants of these bacteria that lack specific glycoside hydrolases predicted from whole-genome sequences. We anticipate that growth studies performed with well-characterized wildtype and glycoside hydrolase-deficient mutants, individually and in co-cultures, will provide new insight into the underlying basis of dental plaque development, opening new approaches for prevention, diagnosis or treatment of plaque-associated oral diseases.

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National Institute of Dental & Craniofacial Research
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Yang, Jinghua; Zhou, Yuan; Zhang, Luxia et al. (2016) Cell Surface Glycoside Hydrolases of Streptococcus gordonii Promote Growth in Saliva. Appl Environ Microbiol 82:5278-86
Zhou, Yuan; Yang, Jinghua; Zhang, Luxia et al. (2016) Differential Utilization of Basic Proline-Rich Glycoproteins during Growth of Oral Bacteria in Saliva. Appl Environ Microbiol 82:5249-58
Bush, C Allen; Yang, Jinghua; Yu, Bingwu et al. (2014) Chemical structures of Streptococcus pneumoniae capsular polysaccharide type 39 (CPS39), CPS47F, and CPS34 characterized by nuclear magnetic resonance spectroscopy and their relation to CPS10A. J Bacteriol 196:3271-8
Ruhl, Stefan; Eidt, Andreas; Melzl, Holger et al. (2014) Probing of microbial biofilm communities for coadhesion partners. Appl Environ Microbiol 80:6583-90
Yang, J; Yoshida, Y; Cisar, J O (2014) Genetic basis of coaggregation receptor polysaccharide biosynthesis in Streptococcus sanguinis and related species. Mol Oral Microbiol 29:24-31
Xu, Deqi; Cisar, John O; Poly, Frédéric et al. (2013) Genome Sequence of Salmonella enterica Serovar Typhi Oral Vaccine Strain Ty21a. Genome Announc 1:
Wu, Chenggang; Mishra, Arunima; Yang, Jinghua et al. (2011) Dual function of a tip fimbrillin of Actinomyces in fimbrial assembly and receptor binding. J Bacteriol 193:3197-206
Yang, Jinghua; Nahm, Moon H; Bush, C Allen et al. (2011) Comparative structural and molecular characterization of Streptococcus pneumoniae capsular polysaccharide serogroup 10. J Biol Chem 286:35813-22
Mishra, Arunima; Devarajan, Bharanidharan; Reardon, Melissa E et al. (2011) Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development. Mol Microbiol 81:1205-20
Yang, Jinghua; Cisar, John O; Bush, C Allen (2011) Structure of type 3Gn coaggregation receptor polysaccharide from Streptococcus cristatus LS4. Carbohydr Res 346:1342-6

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