# Regulation of cyst formation in the AIDS opportunistic pathogen Toxoplasma

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $190,810

## Abstract

PROJECT SUMMARY
Toxoplasma gondii is an intracellular protozoan parasite that poses a major threat to patients
with HIV/AIDS. The replicative stage (tachyzoite) develops into a latent stage (bradyzoite) that
resides inside host cells as cysts in brain, heart, and skeletal muscle tissues. Tissue cysts
remain in the host for life, as they are impervious to the immune response and currently
approved drugs, and give rise to recurrent reactivation of infection in immune compromised
patients. Despite its clinical importance, little is known about the complex transition from the
tachyzoite to bradyzoite stage. A key transcription factor called BFD1 was recently discovered
that is necessary and sufficient for cyst formation in vitro and in mice, but we currently know
nothing about the regulation this factor. We will fill this gap in our knowledge building from our
strong preliminary findings that BFD1 is subject to tight regulatory control at the post-
transcriptional level. We have shown that translation of BFD1 mRNA is enhanced more than 30-
fold in response to TgIF2α phosphorylation. Consistent with this observation is the presence of
numerous upstream open reading frames (uORFs) in the 5’-leader of BFD1 mRNA. Aim 1 will
test our hypothesis that these uORFs play a key role in the preferential translation of BFD1 that
occurs in response to bradyzoite induction. In addition to translational control, we have
additional preliminary data suggesting that BFD1 is regulated at the protein level through lysine
acetylation. Our acetylome analysis of tachyzoites found that BFD1 is acetylated at lysine 1720
(K1720) and that BFD1 was the top hit in a yeast two-hybrid screen performed with the lysine
acetyltransferase TgGCN5a. Aim 2 will test our hypothesis that TgGCN5a regulates BFD1
through K1720 acetylation using co-immunoprecipitation assays and mutational analysis.
Completion of these two aims will reveal critical new insights into the post-transcriptional
mechanisms that govern BFD1 activity, which promise to serve as novel points of therapeutic
intervention to treat this devastating opportunistic infection in HIV/AIDS patients.

## Key facts

- **NIH application ID:** 10401525
- **Project number:** 1R21AI167662-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** William J Sullivan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,810
- **Award type:** 1
- **Project period:** 2021-11-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401525

## Citation

> US National Institutes of Health, RePORTER application 10401525, Regulation of cyst formation in the AIDS opportunistic pathogen Toxoplasma (1R21AI167662-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10401525. Licensed CC0.

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