# Parasite autophagy as a key survival mechanism for the AIDS-associated pathogen Toxoplasma gondii

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $456,477

## Abstract

Reactivation of chronic Toxoplasma gondii infection causes ocular, cardiac, respiratory, and neurologic disease in immune-deficient individuals. Current treatments fail to eliminate the slow replicating, persistent Toxoplasma bradyzoite cysts that seed reactivation and disease, which manifests most severely as Toxoplasmic encephalitis. Our long-term goal is to identify critical liabilities for disrupting Toxoplasma persistence, thereby eliminating the risk of potentially fatal Toxoplasmic encephalitis in at-risk individuals. Toward this goal, we have recently demonstrated that the viability of bradyzoite cysts in culture and in infected mice critically relies on the parasite having a functional autophagy pathway based on targeted disruption of TgATG9. TgATG9 deficient bradyzoites show markedly reduced autophagy and severe loss of viability in culture and in experimentally infected mice. Since autophagy is necessary for cellular homeostasis, our findings support a new concept of disrupting parasite homeostasis to quell infection. However, little is known about autophagy in Toxoplasma and pursuing this concept requires identifying new and divergent components in the pathway. To meet this need, we will discover novel early components of the autophagy pathway, define how they cooperatively mediate the development of autophagic structures, and determine their contributions to parasite persistence in vitro and in vivo. Completing the proposed studies will provide proof-of-concept that targeting parasite homeostasis is an effective strategy to disrupt persistence.

## Key facts

- **NIH application ID:** 10296195
- **Project number:** 2R01AI120607-06A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Vernon Bruce Carruthers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $456,477
- **Award type:** 2
- **Project period:** 2015-12-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296195

## Citation

> US National Institutes of Health, RePORTER application 10296195, Parasite autophagy as a key survival mechanism for the AIDS-associated pathogen Toxoplasma gondii (2R01AI120607-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10296195. Licensed CC0.

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