# Characterization of a putative metal transport protein in Streptococcus sanguinis

> **NIH NIH F31** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $37,098

## Abstract

Project Summary
Streptococcus sanguinis is an oral bacterium that is normally considered a contributor to good oral health, but
it has also been implicated as a major etiological agent of infective endocarditis (IE). IE is a serious disease
caused by certain bacteria entering the bloodstream through lesions in the oral mucosa during surgery,
mastication, or routine hygiene practices. Bacteria that are capable of binding to the heart valve can then
proliferate, which may lead to congenital heart failure, aneurysm, or stroke. Currently, the only preventative for
IE is the prescription of broad spectrum antibiotics given before dental procedures. With the increase in
antibiotic resistance as well as the possibility of IE from routine hygiene activities, other preventatives are being
investigated. ABC-family manganese transporters have been implicated as virulence factors for streptococcal
IE and thus are putative drug targets. A secondary manganese transporter of S. sanguinis was recently
identified and implicated as contributing to virulence in IE. This transporter is homologous to the ZIP family of
proteins, which are traditionally associated with zinc and iron transport. This study seeks to determine the role
of the secondary transporter through its regulation, as well as to investigate the amino acids responsible for
manganese specificity. Aim 1 of the proposal will assess the regulation of the transporter under various
oxygen, pH, and metal conditions. In Aim 2, the amino acids responsible for metal transport will be identified
using site-directed mutagenesis to mutate specific residues of interest within S. sanguinis. Aim 3 will determine
the metal specificity of the transporter by heterologous production and isolation of the protein, incorporation
into liposomes, and assessment of its uptake specificity towards physiologically relevant transition metals by
inductively coupled plasma mass spectrometry. Through these aims, the role and function of the transporter
will be elucidated, enhancing our understanding of ZIP proteins and manganese-transporting proteins,
especially as they relate to bacterial pathogenesis and oral competitiveness.
Access and training for the appropriate instrumentation will be available for the approaches proposed in these
aims in facilities within the Virginia Commonwealth University (VCU) Philips Institute for Oral Health Research,
Department of Chemistry, and School of Pharmacy, as well as at Purdue University and Harvard University.
Collaborators and mentors at VCU, Purdue University, and Harvard University will provide support and
expertise in microbiology, bioinorganic chemistry, and molecular characterization of membrane proteins. Under
the guidance of faculty members in each of these departments and institutions, this project will enhance the
applicant’s knowledge of bioinorganic chemistry, protein characterization, and gene regulation as they relate to
bacterial metal transport proteins and their contribution t...

## Key facts

- **NIH application ID:** 9852885
- **Project number:** 5F31DE028468-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Tanya Puccio
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,098
- **Award type:** 5
- **Project period:** 2019-01-25 → 2020-12-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852885

## Citation

> US National Institutes of Health, RePORTER application 9852885, Characterization of a putative metal transport protein in Streptococcus sanguinis (5F31DE028468-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9852885. Licensed CC0.

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