# Filifactor alocis interactions with neutrophils

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2022 · $454,075

## Abstract

Abstract
Periodontitis is one of the six most common chronic inflammatory diseases affecting ~ 50% of the adults in the
USA. The etiology of periodontitis is strongly associated with changes in both the microbial composition and
density of an indigenous symbiotic community to a more diverse dysbiotic microbial community. High-throughput
sequencing techniques applied to characterize the composition of the periodontal microbiota obtained from
disease sites, revealed the presence of high number of newly appreciated oral pathogens. Among these is the
Gram-positive anaerobic rod Filifactor alocis, present in high numbers in the oral biofilm of periodontal disease
sites compared to healthy sites. The challenge now is to determine the potential pathogenicity, virulence
mechanisms and possible immune subversion arsenal of F. alocis. The response that the host mounts to the
bacterial challenge plays a major role in disease progression. Neutrophils are the primary leukocyte recruited to
the subgingival crevice and their interaction with the microbial community is a key determinant of oral health
status. Understanding how the host responds to the different microbial challenges will increase our knowledge
of the disease process. The current proposal will test the hypothesis that F. alocis undermines neutrophil effector
functions to promote its survival. We will test our hypothesis by the following specific aims: Aim 1: To define F.
alocis regulation of neutrophil vesicular trafficking to evade killing and promote bacteria colonization and bone
loss. The goal of this aim will be to test the hypothesis that F. alocis manipulates neutrophil signaling pathways
to uncouple the bactericidal activity from the inflammatory response to successfully evade killing. Aim 2: To
characterize F. alocis ability to modulate apoptosis in human neutrophils. The goal of this aim will be to test the
hypothesis that F. alocis modulates neutrophils apoptotic program as a virulence strategy to preserve an
intracellular niche within the neutrophil phagosome. The current project is a collaborative effort from an
investigator who is an expert in the field of neutrophil biology and inflammation and its interactions with emerging
oral pathogens (Dr. Uriarte) and an expert in the field of oral pathogens and host cell responses using in vivo
models of periodontitis (Dr. Lamont). The proposed collaborative efforts offer an innovative and strong framework
to characterize the pathogenic potential of F. alocis. In addition, the data generated from this application will fill
a significant gap in our knowledge and lay the foundation for development of new therapeutic approaches to
combat periodontitis.

## Key facts

- **NIH application ID:** 10458581
- **Project number:** 5R01DE024509-09
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Silvia M Uriarte
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $454,075
- **Award type:** 5
- **Project period:** 2014-07-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458581

## Citation

> US National Institutes of Health, RePORTER application 10458581, Filifactor alocis interactions with neutrophils (5R01DE024509-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458581. Licensed CC0.

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