# Oxidative Stress Resistance Mechanisms in Filifactor Alocis

> **NIH NIH R03** · LOMA LINDA UNIVERSITY · 2021 · $158,000

## Abstract

A. PROJECT SUMMARY/ABSTRACT
 Recent oral microbiome studies have recognized a myriad of as-yet-culturable and fastidious
organisms that have shown a strong correlation with periodontal disease severity. It is likely that the emerging
new pathogens may play a more significant role in the disease compared to the traditional “red complex”
bacteria Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. One such previously
unrecognized organism, Filifactor alocis, is a Gram-positive, asaccharolytic, obligate anaerobic rod. Several
recent studies have found this bacterium at significantly higher levels in adult or refractory periodontitis patients
and have suggested that it could be included as a diagnostic indicator of periodontal disease.
 Currently, there is little or no information on survival mechanisms and virulence of F. alocis.
Primarily, this is due to the unavailability of an efficient genetic system to allow genetic manipulations of the F.
alocis genome. In response to environmental stress, our preliminary studies showed that F. alocis is relatively
more resistant to H2O2-induced oxidative stress compared to P. gingivalis. Also, under H2O2-induced stress
conditions, the survival of P. gingivalis is enhanced more than 4-fold in the presence of F. alocis. These
observations suggest that F. alocis may have the ability to modify/reduce the oxidative stress environment and
stabilize the microbial community of the periodontal pocket. In an RNA-seq analysis, the transcriptional profile
of F. alocis showed that in coculture with P. gingivalis (compared to F. alocis monoculture) under H2O2-induced
stress, the most highly upregulated genes in F. alocis encode for a putative manganese ABC transporter
FA0894-FA0895-FA0896-FA0897. Manganese has been proposed to detoxify reactive oxygen species and
protect bacteria from oxidative stress. It is our hypothesis that the F. alocis hypothetical ATP transporter,
FA0894-FA0897, may play an important role in enhanced protection/survival of P. gingivalis against
H2O2-induced stress. We wish to understand the modulation of F. alocis potential virulence factors in
response to interaction with P. gingivalis and evaluate if they contribute to protection/persistence of P.
gingivalis against the oxidative environment of the periodontal community. The proposed specific aims are: (1)
to evaluate the specific role(s) of F. alocis putative ABC transporter FA0894-FA0897 in the protection/survival
of P. gingivalis under H2O2-induced stress. (2) to develop an efficient genetic system for Filifactor that includes
a markerless, in-frame deletion system and/or transposon mutagenesis system.
 Collectively, the data generated will facilitate a comprehensive assessment of the molecular
mechanism(s) and overall interplay involving F. alocis and the ‘keystone’ pathogen P. gingivalis. It will also
generate a polymicrobial model system that may facilitate the development of novel therapeutic interventions
to aid in the ...

## Key facts

- **NIH application ID:** 10217430
- **Project number:** 1R03DE029825-01A1
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **Principal Investigator:** Arunima Mishra
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $158,000
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217430

## Citation

> US National Institutes of Health, RePORTER application 10217430, Oxidative Stress Resistance Mechanisms in Filifactor Alocis (1R03DE029825-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10217430. Licensed CC0.

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