# MEP pathway resistance in Plasmodium falciparum

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $452,490

## Abstract

PROJECT SUMMARY
Severe malaria due to infection by Plasmodium falciparum is a serious threat to global health with over
a million deaths per year. New antimalarial agents are needed due to widespread resistance to existing
therapies. A promising antimalarial drug target is the MEP pathway of isoprenoid biosynthesis, which
is not found in humans. We have used forward genetic screening to identify malaria parasites resistant
to MEP pathway inhibition. We have thus identified a new family of metabolic regulators in malaria, the
HAD proteins. We now propose to determine the mechanism by which loss of HAD phosphatases
confers drug resistance (Aim 1); establish the biological functions of HADs in parasite development
(Aim 2); and use a new MEP pathway inhibitor to identify and characterize additional mechanisms of
resistance (Aim 3). We will identify P. falciparum genes and pathways that genetically interact with the
essential MEP pathway and our strong preliminary results support this approach. In addition, our results
will inform our understanding of the basic biology of the HAD family of metabolic regulators and will
determine whether HAD-mediated drug resistance can be transmitted.

## Key facts

- **NIH application ID:** 10824298
- **Project number:** 5R01AI103280-12
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Audrey Ragan Odom John
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $452,490
- **Award type:** 5
- **Project period:** 2012-12-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824298

## Citation

> US National Institutes of Health, RePORTER application 10824298, MEP pathway resistance in Plasmodium falciparum (5R01AI103280-12). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10824298. Licensed CC0.

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