Among many other contributions to oral health, saliva helps to maintain an ecological balance within the diverse oral biofilm microbiota through fostering colonization by harmless commensal bacteria. Because the oral cavity serves as a port of entry for pathogenic microorganisms to both gastrointestinal and respiratory tracts, legitimate interest exists to dissect salivary components that interact with commensal bacteria from those that are bound by putative extraoral pathogens. Preliminary data suggest that there exists additional not yet well understood complexity in the structural presentation or substitution of sialic acids on salivary glycoproteins that are likely to influence adhesin-mediated bacterial binding by both, commensal oral streptococci and extraoral pathogens. Considering that more than 40 different structural subtypes of sialic acids exist in nature and are known to mediate a wide variety of physiological and pathological processes, including recognition by viruses and other pathogens, thus far little work has been done to determine which structural sialic acid subtypes are present on glycoproteins in human saliva, and which are specifically recognized by oral commensal streptococci in comparison to sialic acid binding pathogens such as H. pylori or S. pneumoniae. We hypothesize that sialic acid substitution by O-acetyl groups influences streptococcal binding. The results are expected to shed additional light on the surprisingly narrow tissue and host tropism of certain viridans streptococci, of which some thrive exclusively within the human oral cavity. Identification of the structural requirements for bacterial binding to sialic acids will be relevant not only to saliva and susceptibility to oral diseases, such as caries and periodontitis, but may also be readily applied to the interaction of pathogenic microorganisms with other bodily secretions and mucous-covered epithelia in respiratory, digestive and genital tracts. Moreover, once the exact sialic acid recognition motifs for certain microbial adhesins are determined, it will become possible to design carbohydrate analogues as drugs to prevent colonization by undesired bacteria.
The specific aims of the project are to: 1. Define how 9-O-acetylated sialic acids are distributed among members of the 2-D salivary glycoproteome. 2. Determine the structural subtypes of sialic acids recognized by the corresponding adhesins and demonstrate that 9-O-acetylation of sialic acids determines streptococcal binding to salivary glycoproteins.
These aims will be achieved by a combination of glycobiological and proteomics methods.

Public Health Relevance

The proposed study sets out to add significance to the oral cavity being a main way of entry to both gastrointestinal and respiratory tracts by investigating the discriminating role of saliva in fostering oral colonization by a beneficial commensal microflora versus preventing infection by pathogenic microorganisms. This research is relevant to human health because the findings are expected to ultimately help understand tissue tropism of bacteria to the mouth and other mucus-lined tissues. Deciphering the molecular mechanisms underlying this tropism is expected to pave the way for future pharmacological prevention of colonization by undesired bacteria.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Burgoon, Penny W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
State University of New York at Buffalo
Schools of Dentistry
United States
Zip Code
Cross, Benjamin W; Ruhl, Stefan (2018) Glycan recognition at the saliva - oral microbiome interface. Cell Immunol 333:19-33
Xu, Duo; Pavlidis, Pavlos; Taskent, Recep Ozgur et al. (2017) Archaic Hominin Introgression in Africa Contributes to Functional Salivary MUC7 Genetic Variation. Mol Biol Evol 34:2704-2715
Thamadilok, S; Roche-HÃ¥kansson, H; HÃ¥kansson, A P et al. (2016) Absence of capsule reveals glycan-mediated binding and recognition of salivary mucin MUC7 by Streptococcus pneumoniae. Mol Oral Microbiol 31:175-88
Xu, Duo; Pavlidis, Pavlos; Thamadilok, Supaporn et al. (2016) Recent evolution of the salivary mucin MUC7. Sci Rep 6:31791
Baker, O J; Edgerton, M; Kramer, J M et al. (2014) Saliva-microbe interactions and salivary gland dysfunction. Adv Dent Res 26:7-14
Ruhl, Stefan; Eidt, Andreas; Melzl, Holger et al. (2014) Probing of microbial biofilm communities for coadhesion partners. Appl Environ Microbiol 80:6583-90
Deng, Lingquan; Bensing, Barbara A; Thamadilok, Supaporn et al. (2014) Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood. PLoS Pathog 10:e1004540
Heo, Seok-Mo; Ruhl, Stefan; Scannapieco, Frank A (2013) Implications of salivary protein binding to commensal and pathogenic bacteria. J Oral Biosci 55:169-174
Heo, Seok-Mo; Choi, Kyoung-Soo; Kazim, Latif A et al. (2013) Host defense proteins derived from human saliva bind to Staphylococcus aureus. Infect Immun 81:1364-73
Ruhl, Stefan (2012) The scientific exploration of saliva in the post-proteomic era: from database back to basic function. Expert Rev Proteomics 9:85-96

Showing the most recent 10 out of 11 publications