# Exploitation of the host immune response by Aggregatibacter actinomycetemcomitans mediated by QseBC

> **NIH NIH F31** · UNIVERSITY OF LOUISVILLE · 2022 · $34,004

## Abstract

Aggregatibacter actinomycetemcomitans (Aa) has been strongly associated with localized aggressive
periodontitis (1-3). At the anaerobic environment of the sub-gingival pocket Aa is exposed to changes in
homeostasis, yet little is known about the processes used by Aa to acquire the necessary nutrients such as:
iron, in order to adjust to changes and persist. The study the mechanism used by Aa to sense and respond to
environmental stress is essential in order to to develop therapeutic treatments for periodontal disease and
further the knowledge in the field of microbial endocrinology. A two component system (TCS), known as
QseBC, is expressed by Aa and it plays an important role in the process of adaptation and survival in the
anaerobic environment. The sensor molecule QseC was found to play a role in growth and virulence of Aa (1).
Further, the signals responsible for the activation of this TCS were identified as being catecholamines and iron
(CAT-Fe) (Weigel 2015). The protein YgiW, has no known function and it is co-expressed with the QseBC
TCS. The regulation of the enterobactin operon genes were found to remain unchanged in the presence of
CAT-Fe (Weigel 2015), when other genes involved in iron uptake were downregulated, suggesting that it must
play an important role for Aa persistence in the anaerobic environment. Among the four genes encoded in the
enterobactin operon there is an outer membrane enterobactin receptor, FepA (4), yet Aa does not produce
siderophores (5). Localized aggressive periodontitis promotes increased infiltration of polymorphonuclear
(PMNs) leukocytes or neutrophils (6). PMNs have been shown to release catecholamines (CAT), a type of
siderophore, suggesting that the inflamed sub-gingival pocket may serve as a CAT-Fe rich environment.
Therefore, the proposed hypothesis is that Aa utilizes catecholamines from the host environment and via
QseBC, priming metabolism for growth in the anaerobic sub-gingival environment, and then acquiring
iron through the uptake of CAT-Fe via the enterobactin complex. The hypothesis will be tested by
addressing the following aims: 1) to characterize the synthesis, storage and release of CAT by PMNs
stimulated with Aa, 2) to define the interaction of CAT-Fe with QseC and/or YigiW, and 3) determine the
contribution of YgiW on QseC activation. The research design will consist of exposing human PMNs directly to
wild type and virulence factors mutants of Aa and measuring CAT levels by ELISA to confirm their ability to
release CAT (Aim 1a) and identify the signals required for their release (Aim 1b). The granules of PMNs will
be isolated and screened using CAT antibodies, to identify where CAT are stored (Aim 1c). Next, biding kinetic
analysis will be used to characterize the interaction of CAT-Fe to QseC and/or YgiW (Aim 2a) and surface
plasmon resonance will be used to define YgiW contribution to QseC activation (Aim 2b). Lastly, binding
kinetic analysis will be employed to determine the binding i...

## Key facts

- **NIH application ID:** 10327300
- **Project number:** 5F31DE027585-05
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Hazel Ozuna
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,004
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327300

## Citation

> US National Institutes of Health, RePORTER application 10327300, Exploitation of the host immune response by Aggregatibacter actinomycetemcomitans mediated by QseBC (5F31DE027585-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10327300. Licensed CC0.

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