# Microneme function in Toxoplasma

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $390,000

## Abstract

Abstract
Exit from host cells is an essential step in the life cycle of intracellular pathogens
including Toxoplasma gondii, the agent of human toxoplasmosis. Related malaria
parasites also egress from host cells after replication, and they additionally traverse cells
by escaping from a transient vacuole in a manner similar to egress. Recent work has
identified critical roles for pore-forming proteins and phospholipases in cell egress and
traversal. But how these proteins facilitate egress and the extent to which they
collaborate to disrupt membranes is unknown. Also, although recent reports suggest that
acidification of the parasite-containing vacuole augments activity of the pore-forming
protein(s), the proton pumps mediating acidification have not been identified. Precisely
how acidification facilitates pore-formation and egress is also unclear. The absence of
such knowledge precludes rationale design of interference strategies to alter the course
of infection and disease. We will address these key gaps by identifying the proton
pump(s) responsible for vacuole acidification (Aim1), defining the structural basis for pH-
augmented membrane binding by the pore-forming protein Perforin-Like Protein 1 (Aim
2), and measuring pH-dependent cooperativity between Perforin-Like Protein 1 and an
LCAT phospholipase for membrane disruption during egress. The proposed studies will
advance the field by delivering insight that is broadly relevant to egress by apicomplexan
parasites and other cytolytic pathogens.

## Key facts

- **NIH application ID:** 9914201
- **Project number:** 5R01AI046675-20
- **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:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 1999-12-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914201

## Citation

> US National Institutes of Health, RePORTER application 9914201, Microneme function in Toxoplasma (5R01AI046675-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9914201. Licensed CC0.

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