# RP-Riestra/Sussman: Investigating the Antibacterial and Immune Modulating Effects of Trichomonas Vaginalis Infection and Pyroptosis

> **NIH NIH U54** · SAN DIEGO STATE UNIVERSITY · 2024 · $319,460

## Abstract

RESEARCH PROJECT-RIESTRA/SUSSMAN - Project Summary
The public health threat posed by infection with the sexually transmitted parasite Trichomonas vaginalis, its
disproportionate affliction of racial and ethnic minorities, and its vastly understudied status have led to
classification of trichomoniasis as one of our country’s most neglected parasitic infection. The first part of this
research project will investigate the molecular mechanisms by which T. vaginalis kills Lactobacillus crispatus
and Lactobacillus iners-cervicovaginal bacteria that generally have a protective role in the female reproductive
tract. Specifically, we will observe the parasite-lactobacilli interactions using live/dead staining and assess the
dynamics of bacterial killing. Using pharmacological inhibitors and by generation of clathrin light chain knockout
parasites, we will determine the contribution of phagocytosis towards T. vaginalis antibacterial activity. A
second part of our project will assess if T. vaginalis infection-mediated activation of the inflammatory cell death
called pyroptosis leads to indirect antibacterial effects against lactobacilli. Specifically, we will test whether a
recombinant form of the gasdermin D N-terminal cleavage fragment has antibacterial effects against lactobacilli
that constitute the different cervicovaginal microbial communities present in women. Additionally, using
ectocervical gasdermin D knockout cells we will further delineate how induction of pyroptotic cell death during
T. vaginalis infection contributes to killing of cervicovaginal lactobacilli, and whether killing of these protective
bacteria results in increased inflammation. Lastly, we will investigate the interaction of T. vaginalis with L.
crispatus, L. iners, and human vaginal cells using a vagina-on-a-chip model. Indirect immunofluorescence
assays of these chips will reveal the spatial organization of these microbes on stratified vaginal epithelium. We
will also quantify the differential viability of each microbe upon triad interaction compared to colonization with
each single microbe. Lastly, we will profile differences in secretion of inflammasome-mediated cytokines and
processed gasdermin D release. Together, our work will elucidate how T. vaginalis exerts antibacterial effects
during infection and how it mechanistically promotes inflammation, processes that are associated with
increased predisposition of women to adverse health effects and which are currently untreated with standard
trichomoniasis treatment. Our research efforts could thus help guide the development of future targeted
therapeutics to ameliorate the impact of T. vaginalis infection, particularly those from lower socioeconomic and
underrepresented backgrounds disproportionately affected by T. vaginalis infection.

## Key facts

- **NIH application ID:** 11002225
- **Project number:** 2U54MD012397-06A1
- **Recipient organization:** SAN DIEGO STATE UNIVERSITY
- **Principal Investigator:** Angelica M Riestra
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $319,460
- **Award type:** 2
- **Project period:** 2018-09-11 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11002225

## Citation

> US National Institutes of Health, RePORTER application 11002225, RP-Riestra/Sussman: Investigating the Antibacterial and Immune Modulating Effects of Trichomonas Vaginalis Infection and Pyroptosis (2U54MD012397-06A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11002225. Licensed CC0.

---

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