# Outer Membrane Proteins of Pathogenic Oral Treponemes Inhibit Actin Rearrangement and Antimicrobial Functions of Neutrophils

> **NIH NIH F31** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $31,724

## Abstract

Periodontal disease is a bacterially induced inflammatory condition affecting 47% of adults in the United States
and is the number one cause of tooth loss worldwide. This condition is characterized by the destruction of
tooth-supporting structures resulting from dysbiosis between the host immune system and the normally
commensal oral biofilm. Treponema denticola, Treponema maltophilium, and Treponema lecithinolyticum are
three understudied bacterial species abundant in the polymicrobial biofilm associated with severe periodontal
disease, and a complete understanding of their pathogenic properties is lacking. T. denticola, the most-well-
studied oral spirochete, has a prominent virulence factor: the major outer sheath protein (Msp) that
dysregulates the functions of host cells, including neutrophils. T. maltophilium and T. lecithinolyticum have
Msp-like outer membrane proteins called MspA and MspTL, respectively. Neutrophils are key innate immune
cells that protect oral tissues from pathogenic bacteria by coordinating cellular signaling, structural elements,
and cell function. Msp inhibits neutrophil function by disrupting the balance of phosphoinositides, cellular lipid
metabolites key for intracellular signaling. This disruption involves altered regulation of the PI3 kinase (PI3K)
and phosphatase and tensin homolog (PTEN) axis, leading to inappropriate remodeling of the actin
cytoskeleton, impaired chemotaxis, and altered functioning of neutrophils. A remaining gap in our knowledge is
how these understudied Treponema proteins modulate actin dynamics to impair other crucial neutrophil
properties. The overall objective of this project is to characterize how these Treponema species and their
surface proteins manipulate neutrophil cytoskeleton signaling pathways and granule release to promote
survival. We hypothesize that Msp-like proteins dysregulate actin remodeling in neutrophils to promote bacterial
survival. To test this hypothesis, this project aims to (1) characterize the effects of Msp proteins on the
PI3K/PTEN axis and actin branching dynamics and (2) assess the ability of Treponema species and their Msp
proteins to promote survival by modulating neutrophil recruitment and degranulation. To achieve these aims, I
will utilize a variety of methods, including analyses of actin incorporation, immunological techniques,
microscopy, flow cytometry, animal models, molecular biology, and microbiological techniques. Completion of
this project will provide valuable insight into the interactions between spirochetes and the immune system and
how these relationships drive disease progression. The mentoring and training plan to be performed within the
multidisciplinary research environment at the University at Buffalo will provide me with the scientific and
professional development skills necessary to successfully transition to the next stage of a successful research
career.

## Key facts

- **NIH application ID:** 10233602
- **Project number:** 1F31DE030705-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Natalie Anselmi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,724
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233602

## Citation

> US National Institutes of Health, RePORTER application 10233602, Outer Membrane Proteins of Pathogenic Oral Treponemes Inhibit Actin Rearrangement and Antimicrobial Functions of Neutrophils (1F31DE030705-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10233602. Licensed CC0.

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