# Defining a novel strategy of adhesion to host carbohydrates employed by Streptococcus oralis

> **NIH NIH R21** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $191,824

## Abstract

Project Summary:
Adhesion is a critical step in development of infective endocarditis (IE). However, despite Streptococcus oralis
being a common cause of sub-acute IE there are no defined adhesion mechanisms for this species. Ultimately,
filling this gap in knowledge may lead to strategies to reduce the burden of IE. Other bacterial species bind
terminal carbohydrates or glycosidase exposed cryptic carbohydrates. Preliminary data suggest that in order to
maintain adhesion to host surfaces, despite production of a glycosidase that cleaves the terminal receptor, S.
oralis has adopted a novel strategy that simultaneously uses both terminal and cryptic receptors. These data
show that S. oralis binds platelets via terminal sialic acid and underlying β-1,4 linked galactose, which is only
exposed upon cleavage of terminal sialic acid by S. oralis neuraminidase. Given the broad distribution of these
carbohydrates, it is likely that this adhesion mechanism contributes to S. oralis binding to multiple IE-relevant
host components and that these interactions are critical to disease development. This strategy of
simultaneously binding terminal and cryptic receptors is likely used by other glycosidase positive species and
by glycosidase negative species during polymicrobial infections. Adhesion to both carbohydrates requires a
serine rich repeat protein Fap1. This is the first example of a serine rich repeat protein required to bind β-1,4
linked galactose and two distinct carbohydrate receptors. These data lead to the hypothesis that in order for
neuraminidase producing S. oralis to maintain adhesion to host surfaces during development of IE,
this species employs a novel strategy of simultaneously binding terminal sialic acid and
neuraminidase exposed β-1,4 linked galactose and that the SRRP Fap1 directly binds these
carbohydrates. Three Aims will test this hypothesis. Aim 1: Determine the ability of Fap1 to directly bind
sialic acid and β-1,4 linked galactose. Preliminary data lead us to hypothesize that Fap1 directly binds sialic
acid and β-1,4 linked galactose. Studies will further define the role of Fap1 in adhesion by determining the
ability of this adhesin to directly bind these carbohydrates, the specific carbohydrate structures bound and the
strength of these interactions. Aim 2: Determine the role of Fap1 in binding other IE relevant host
components. Most preliminary data was generated using platelets; however, adhesion to other host
components on the damaged valve is also likely important in pathogenesis. Given that glycan structures
containing sialic acid and β-1,4 linked galactose are common on host cells and proteins, this aim will test the
hypothesis that Fap1-dependent adhesion to these carbohydrates is a conserved mechanism for binding host
components present on damaged valves. Aim 3: Determine the contribution of Fap1 to IE using a 3D
microvessel model. A cutting edge 3D microvessel model will be adapted to study the contribution of Fap1-
medi...

## Key facts

- **NIH application ID:** 9877393
- **Project number:** 1R21AI149414-01
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Samantha Jane King
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,824
- **Award type:** 1
- **Project period:** 2020-03-10 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877393

## Citation

> US National Institutes of Health, RePORTER application 9877393, Defining a novel strategy of adhesion to host carbohydrates employed by Streptococcus oralis (1R21AI149414-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9877393. Licensed CC0.

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