# The role of oral spirochete virulence factors in the impairment of neutrophil response

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $378,813

## Abstract

Oral spirochetes are present at high abundance in the subgingival dental plaque associated with
severe periodontal lesions. Periodontitis affects up to 47% of the United States population in
some form. Treponema denticola and other oral Treponema species colonize and thrive at the
plaque-gingival tissue interface, in close association with neutrophils, the primary innate
immune cells involved in the gingival tissue host response. The major outer sheath protein
(Msp) is a prominent virulence factor produced by Treponema denticola that directly impairs
neutrophil chemotaxis in vitro by modulation of lipid metabolites responsible for initiating the
chemotactic process, mediated by active epitopes in the Msp protein. Many bacterial pathogens
including oral spirochetes are known to produce outer membrane vesicles (OMVs) loaded with
many bacterial components; including pathogenic membrane protein, such as Msp. OMVs are
also now recognized as potent packages of virulence factors actively produced during infection
with local and far-reaching pathogenic effects due to their small size and properties; which play
key roles in bacterial survival and modulation of host response. However, there is still a
significant gap in knowledge of the role of Msp in vivo as well as the functional and biological
contribution of other oral Treponema species and OMVs in manipulating the neutrophil immune
response. Likewise, there is a lack of efficient therapeutic molecules directed towards crucial
spirochete virulence factors. Our central hypothesis is that oral spirochetes mediate impairment
of neutrophil function through virulence factors with common functional properties. We will test
our hypothesis by completion of the following specific aims: 1. Determine the potential of T.
denticola Msp and the active epitopes to modulate neutrophil function in rodent-models of
inflammation and periodontal disease 2. Assess Msp-like proteins from understudied oral
spirochetes as novel virulence factors to impair neutrophil function and 3. Assess biogenesis of
T. denticola OMVs as prominent virulence factors to impair neutrophil function. This work will
advance our understanding of spirochete pathogenicity by examining common functionality of
Msp proteins across oral treponema species, provide novel insight into the contribution of OMVs
and the role of Msp in OMV function and interaction with neutrophils. Further, we also propose
to develop potential therapeutic reagents directed towards Msp. Understanding how oral
spirochete virulence factors render the neutrophil immune response ineffective and
development of novel therapeutic tools to prevent this, is crucial to improving oral health.
!

## Key facts

- **NIH application ID:** 10229624
- **Project number:** 5R01DE027073-04
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Michelle B Visser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,813
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229624

## Citation

> US National Institutes of Health, RePORTER application 10229624, The role of oral spirochete virulence factors in the impairment of neutrophil response (5R01DE027073-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10229624. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*