Binding specificity and transcriptional regulation of antigen I/II adhesins in Streptococcus gordonii

Project Summary/Abstract
Bacterial expression of cell surface-associated adhesin proteins facilitates the formation of biofilms. Dental
plaque is a polymicrobial biofilm of the human mouth that contributes to oral infectious diseases. Formation of
this dental biofilm is initiated by pioneer colonization, whereby Streptococcus species use adhesin proteins to
attach to the saliva-coated tooth surface. Among the many adhesins expressed by Streptococci, the antigen type
I/II (AgI/II) adhesin family is widely conserved and has been shown to mediate interactions with several host
molecules and other oral microbes. This proposal uses Streptococcus gordonii as a model to investigate the role
of AgI/II adhesins in host surface attachment and biofilm development. S. gordonii is an oral commensal that
expresses two AgI/II adhesins: SspA and SspB (SspA/B). Evidence shows that SspA/B is necessary for
attachment to salivary mucin 5B (MUC5B)-coated surfaces. Proposed experiments will investigate binding
between SspA/B proteins and MUC5B glycans. The variable (V) regions of SspA and SspB are expected to
differentially bind the O-glycans decorating the MUC5B peptide backbone, contributing to initial attachment.
SspA/B expression decreases, however, as the biofilm matures, suggesting that transcriptional regulation of
sspA/B is complex. Data suggests that after initial surface attachment, protein acetylation regulates sspAB
expression via the two-component system BfrAB. Therefore, genetic approaches are proposed to investigate
the role of protein acetylation in sspA/B gene transcription. Overall, these studies will show that S. gordonii AgI/II
adhesins mediate binding to MUC5B and are transcriptionally regulated by acetylation of the BfrB sensor kinase.
Findings may be broadly applicable to streptococcal AgI/II adhesins and may suggest new mechanisms to
control microbial community development in health and in streptococcal disease.

Grant Number: 5F30DE033234-03
NIH Institute/Center: NIH
Principal Investigator: Sarah Aitken