# Regulation of Surface Protein Presentation on Streptococcus gordonii

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $357,554

## Abstract

Bacteria alter gene expression while adapting to their environments. In some cases, gene
expression changes in response to contact with abiotic surfaces. We show that Streptococcus
gordonii, a model Gram-positive commensal bacterium, appears to regulate surface protein
presentation in response to specifically engaging MUC5B. During biofilm formation on MUC5B,
presentation of SGO_0707 on the cell wall and down-regulation of SGO_0890 and SGO_1487
depend on an intramembrane two-component system (TCS) sensor (SGO_1180). We also report
(preliminary data) that the well-studied paired adhesins, SspA and SspB (SspAB), is also required to
signal for presentation of SGO_0707 and loss of SGO_0890 and SGO_1487. Somewhat
promiscuous in specificity, SspAB binds MUC5B. Hence, SspAB may serve as a receptor to induce
an outside-in signal. Since SspAB covalently attaches to the cell wall, the signal to the cell
membrane is probably transduced by another associated macromolecule. S. gordonii lipoteichoic
acid (LTA) binds high molecular weight mucins, interacts with cell wall proteins, and traverses the
cell wall to intercalate with the outer leaflet of the cell membrane. Preventing D-alanylation of S.
gordonii LTA causes altered presentation of surface proteins. These data suggest that LTA and
SspAB are co-receptors for MUC5B, with LTA serving to transduce a signal to a TCS (SGO_1180
and SGO_1181) to change the surface proteins presented on S. gordonii. We hypothesize,
therefore, that S. gordonii SspAB cooperates with LTA to serve as a model signal transducing
receptor for MUC5B during biofilm formation. To test our hypothesis and satisfy criteria for an
outside-in signaling receptor, we will (1) determine whether both SspA and SspB are required; (2)
show whether LTA functions as a co-receptor; (3) characterize response regulator SGO_1181 for
signaling and regulation; (4) determine whether the change in surface protein presentation involves
transcriptional and post-translational mechanisms; and (5) determine whether SspAB and
SGO_1180 signal through intersecting or parallel pathways by performing comparative
transcriptome analysis. To characterize the output of receptor signaling (Aims 1-4), we will measure
transcription of sentinel genes (i.e., SspA, SspB, SGO_0707, SGO_0890, SGO_1487 and
SGO_1180), presentation of sentinel surface proteins (i.e., 0707, 0890, 1487), and 1180
phosphorylation dependence. These experiments will define outside-in signaling in S. gordonii in
response to specific surface environmental cues, which had been previously been viewed as a
feature of higher organisms. This knowledge could suggest how certain bacteria adapt to changing
environments when they must adhere or die.

## Key facts

- **NIH application ID:** 9981418
- **Project number:** 5R01DE025618-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** MARK C HERZBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,554
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981418

## Citation

> US National Institutes of Health, RePORTER application 9981418, Regulation of Surface Protein Presentation on Streptococcus gordonii (5R01DE025618-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9981418. Licensed CC0.

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