Title: 0166 - Oral Streptococcal Binding to Complex Host Sialoglycoproteins
Benjamin Cross (Presenter)
University at Buffalo
Supraporn Thamadilok, University at Buffalo
Zahra Khedri, University of California
Lingquan Deng, University of California
Xi Chen, University of California
Tina Iverson, Vanderbilt University
M. Vickerman, University at Buffalo
Hervé Tettelin, University of Maryland
Ajit Varki, University of California
Stefan Ruhl, University at Buffalo
Objectives: Many oral streptococci express serine-rich repeat proteins (SRRP) that extend away from the cell surface to present adhesin domains that bind to various ligands including glycans bearing sialic acids. SRRPs bind to salivary glycoproteins in the oral cavity, platelet glycoproteins in the blood, and other host sialoglycoproteins. We recently discovered streptococci isolated from human hosts that preferentially bind to the sialic acid N-glycolylneuraminic acid (Neu5Gc) on microarrays presenting short sialoglycans. This is surprising because, in contrast to most mammals, humans are only able to produce N-acetylneuraminic acid (Neu5Ac). Are these Neu5Gc-binding streptococcal human isolates unable to bind human glycoproteins? Here we test the binding preferences of the human isolates against various natural glycoproteins in addition to structurally defined glycan chains on a microarray.
Methods: Streptococcus gordonii and S. sanguinis strains selected for this study include Neu5Ac-preferring strains, Neu5Gc-preferring strains, and strains able to bind both Neu5Ac and Neu5Gc as shown by sialoglycan arrays. Mutant strains deficient in SRRP expression were also included. Purified natural glycoproteins of human (Neu5Ac) and animal (Neu5Ac and Neu5Gc) origin were immobilized as dot blots and tested for bacterial binding by the bacteria overlay method.
Results: Bacterial binding to some glycoproteins correlates with the expected Neu5Ac or Neu5Gc preference, but most binding phenotypes are more complex. Each tested strain displays a unique binding pattern that was not entirely predictable based on the sialoglycan microarray data.
Conclusions: Sialoglycan microarray binding studies provide crucial, molecularly defined information about binding specificities of the streptococci tested. However, binding patterns of these bacteria to natural sialoglycoproteins appear to be more complex. This may be due to changes in avidity based on density, steric presentation, or unknown modifications of sialoglycans on glycoproteins. Future experiments will be conducted with purified recombinant SRRP binding regions to reduce complications from other confounding elements of the bacterial cell surface.
This abstract is based on research that was funded entirely or partially by an outside source:
NIDCR, R01DE019807 and R21DE025826 (S.R.); NIGMS, R01GM32373; NIAID, R01AI106987
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: None