# FOSMIDOMYCIN RESISTANCE IN PLASMODIUM FALCIPARUM

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $423,000

## 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. This pathway is
the target of an antimalarial agent, fosmidomycin, which is currently in Phase II clinical
trials in combination therapies for malaria. We have used forward genetic screening to
identify fosmidomycin-resistant malaria parasites, in order to investigate the genetic
mechanisms of fosmidomycin resistance and advance our basic understanding of
isoprenoid biology. We have thus identified a new family of metabolic regulators in
malaria, the HAD proteins. Our approach consists of two specific aims: (1) Establish the
mechanisms of HAD-mediated drug resistance, and (2) Characterize the genetic and
metabolic mechanisms that underlie enhanced drug resistance in malaria strains lacking
HADs. We will identify P. falciparum genes and pathways that genetically interact with
the essential MEP pathway and our strong preliminary results support this approach.
Our results will identify molecular biomarkers of fosmidomycin resistance and identify
new targets for much needed antimalarial drug development.

## Key facts

- **NIH application ID:** 10058237
- **Project number:** 5R01AI103280-09
- **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:** 2021
- **Award amount:** $423,000
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058237

## Citation

> US National Institutes of Health, RePORTER application 10058237, FOSMIDOMYCIN RESISTANCE IN PLASMODIUM FALCIPARUM (5R01AI103280-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058237. Licensed CC0.

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