# Exploring Integrative Conjugative Elements in the Biology and Ecology of Oral Streptococci

> **NIH NIH R03** · ARKANSAS STATE UNIVERSITY · 2022 · $139,730

## Abstract

Project Summary
Essential genes represent the most critical components of a bacterial genome and are required for survival. In
recent years, we developed technologies that allowed us to identify and study essential genes in the dental
caries pathogen Streptococcus mutans. Through these studies we have identified several genes that have
unknown functions and yet, are clearly indispensable for the normal physiology of S. mutans. One of these
genes, that we are provisionally naming erfR (essential regulatory factor), is annotated as a transcriptional
regulator. Silencing of this gene causes severe growth and cell morphology defects, suggesting that we have
identified a new and unique regulatory component of S. mutans biology. Notably, this regulatory protein is also
present in the genome of other pathogens, including Group A and Group B streptococci. Since its discovery we
have made advances that show that ErfR regulates the expression of a putative integrative conjugative
element (ICE) known as TnSmu1. These elements participate in the horizontal transfer of genetic material, and
can carry desirable traits such as antimicrobial resistance, and virulence-associated genes. ICEs could be an
important mechanism driving genotypic and phenotypic diversity of this pathogen. However, there is little to no
in-depth characterization of these elements in Sm. To address this knowledge gap we will exploit TnSmu1 and
its regulation by ErfR as a model ICE and have developed three Specific Aims: 1) Functional analysis of
TnSmu1 essentiality and potential for horizontal transfer; 2) Identify genes and metabolic activities controlled
by TnSmu1 induction by transcriptome analysis; 3) Examine the impact of ICEs on Sm host fitness and
evolution. Combined results and conclusions from this proposal will lead to a greater understanding of the
mechanisms of erfR essentiality, TnSmu1 function and physiological effects on Sm, and the broader
distribution of these elements among Sm strains. The outcomes are expected to position erfR/TnSmu1 as an
important model for studying horizontal gene transfer by conjugation in oral bacteria. This will fill a void in our
understanding of these elements in Sm pathogenesis and their impacts on oral biofilm ecology. The proposal
will also contribute to our long-term aspirations in cataloging essential processes in Sm.

## Key facts

- **NIH application ID:** 10426355
- **Project number:** 5R03DE029882-03
- **Recipient organization:** ARKANSAS STATE UNIVERSITY
- **Principal Investigator:** Robert Colquhoun Shields
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $139,730
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426355

## Citation

> US National Institutes of Health, RePORTER application 10426355, Exploring Integrative Conjugative Elements in the Biology and Ecology of Oral Streptococci (5R03DE029882-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10426355. Licensed CC0.

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