# Role of amylopectin granules in chronic toxoplasmosis, an HIV-AIDS defining infection

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2020 · $191,250

## Abstract

Project Summary
A distinguishing characteristic of tissue cyst forming Apicomplexa, like Toxoplasma gondii, is the accumulation
of amylopectin (starch) granules (AG) within bradyzoites and their absence within the actively growing
tachyzoite forms. As polymers of glucose, AG functions as a battery serving as a reserve for energy production
and biosynthetic functions. Our recent work established that bradyzoites retain significant replicative potential
within tissue cysts in vivo. Notably, most bradyzoite replication within tissue cysts occurs asynchronously with
clustered bursts of growth interceded with non-replicative periods. While the specific signals triggering these
bursts remain unknown, what is clear is that they would require substantial energy and metabolite inputs to
execute. Historical evidence and our findings reveal that AG levels within encysted bradyzoites are highly
variable with clusters of parasites lacking AGs adjacent to others that are loaded with starch. This suggests
that AG metabolism involving both synthesis and turnover are active within tissue cysts and may play a central
role in the progression of chronic toxoplasmosis. We will directly address the dynamics and biological
contributions of AGs in the progression of the chronic infection at the level of individual bradyzoites using novel
tools and concepts developed in our recently published work. The variable levels of AG, within encysted
bradyzoites, suggest that both AG accumulation and depletion are under regulatory control. Indeed the
enzymatic machinery required for both the synthesis and regulated turnover of starch are encoded in the
Toxoplasma genome. We will directly test the importance of AG in the acute infection, the regulation of stage
conversion and the establishment/ progression of the chronic infection by targeting the commitment enzyme for
starch synthesis, the UDP-glucose pyrophosphorylase (TgUDP-GPP, TgME49_218200), and the starch
synthase (TgSS, TgME49_222800). Recent evidence suggests that despite being morphologically (though not
biochemically) detectable, amylopectin may play a role in tachyzoite intermediary metabolism as well. In
addition, the contribution of AG's to reactivation, the primary trigger of symptomatic disease in HIV-AIDS will be
addressed in the context of induced immune suppression. With the proposed studies we aim to dissect the
previously unexplored role of AG in tachyzoites, as factors in tachyzoite to bradyzoite conversion, the
progression of the chronic infection and clinically critical reactivation in vivo. These studies will establish the
groundwork for targeting AG metabolism for therapeutic intervention in the chronic infection where the paucity
of effective drugs remains a significant issue in the clinical context of HIV-AIDS.

## Key facts

- **NIH application ID:** 10025481
- **Project number:** 1R21AI150631-01A1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** ANTHONY P. SINAI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,250
- **Award type:** 1
- **Project period:** 2020-03-05 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025481

## Citation

> US National Institutes of Health, RePORTER application 10025481, Role of amylopectin granules in chronic toxoplasmosis, an HIV-AIDS defining infection (1R21AI150631-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10025481. Licensed CC0.

---

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