# FeoA-based Regulation of Pathogenic Ferrous Iron Acquisition

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · 2020 · $172,668

## Abstract

Project Summary
 The acquisition of iron is an essential process for the establishment of virulence among virtually all
pathogens. To fulfill its necessity for this nutrient, the Gram-negative bacterium Porphyromonas gingivalis (the
causative agent of chronic periodontitis) makes use of two main iron uptake pathways to grow and to
proliferate. Under anaerobic conditions, such as those found in subgingival biofilms, P. gingivalis utilizes the
ferrous (Fe2+) iron uptake (Feo) system to import Fe2+. The Feo system is poorly understood at the molecular
and mechanistic levels, but two proteins known as FeoA and FeoB are necessary for ferrous iron uptake in
most pathogens. This proposal seeks to explore the role of FeoA in controlling FeoB function. Based on
preliminary data and previous observations, it is hypothesized that the conserved protein FeoA functions as a
novel, prokaryotic G-protein regulator that is necessary to control the GTP-utilizing, integral membrane protein
FeoB. The P. gingivalis genome offers a unique opportunity to explore the role of FeoA with respect to FeoB,
as the feo operon in this organism indicates that FeoA and FeoB are expressed and function as a single
protein. This proposal outlines a series of biochemical, structural, enzymatic, and in vivo approaches to explore
and to elucidate the potentially novel role of FeoA in controlling Fe2+ transport mediated via FeoB. The results
from these studies have the promise to reveal how FeoA is utilized by the common pathogen P. gingivalis to
fulfill its need for iron. A similar thethered FeoA-FeoB system is predicted to exist in other pathogens implicated
in periodontal disease, such as Tannerella forsythia, Porphyromonas endodontalis, and Porphyromonas gulae.
As such, it is anticipated these results will uncover a general regulatory mechanism present in many oral
pathogens. More broadly, these studies will lay the groundwork for future research to understand how many
pathogens use FeoA in conjunction with FeoB to establish infection. Future studies have the potential to reveal
targets for the development of therapeutic interventions and novel antibiotics.

## Key facts

- **NIH application ID:** 9849763
- **Project number:** 5R21DE027803-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE COUNTY
- **Principal Investigator:** Aaron T Smith
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,668
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849763

## Citation

> US National Institutes of Health, RePORTER application 9849763, FeoA-based Regulation of Pathogenic Ferrous Iron Acquisition (5R21DE027803-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849763. Licensed CC0.

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