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Tag: Plasmodium

Memory regulatory T cells reprogram into protective TFH cell-like effectors in recurrent malaria

Donna Huber on June 22, 2026

Although people living in malaria-endemic areas experience repeated infections with Plasmodium, the role of regulatory T (Treg) cells in recurrent malaria remains poorly understood. During a primary infection with Plasmodium, Treg cells suppress protective immunity by inhibiting germinal center (GC) reactions, thereby impeding the control of parasitemia. In contrast, memory Treg (mTreg) cells remaining after the clearance of initial Plasmodium infection …

The inner membrane complex protein, IMC55, is dispensable for intraerythrocytic development of Plasmodium falciparum

Donna Huber on June 10, 2026

  Plasmodium falciparum, an obligate intracellular Apicomplexan parasite and the causative agent of malaria, must reside and replicate within a host cell during the intraerythrocytic stage. At the end of its replicative cycle, the parasite breaks down two biological membranes using a proteolytic cascade to release invasive daughter cells known as merozoites to continue its asexual …

Structure-Guided Optimization of Novel Inhibitors of Plasmodium Lysyl-tRNA Synthetase with Multistage Activity against Malaria Parasites

Donna Huber on June 2, 2026

A fused dihydropyrrolidino-pyrimidine hit with low lipophilicity and excellent ligand efficiency was identified in a biochemical screen of the Global Health Chemical Diversity Library (GHCDL) against Plasmodium lysyl-tRNA synthetase (KRS). Structure-guided lead optimization delivered analogues with potent parasite growth inhibition, excellent biochemical and cellular selectivity (>1000-fold), and oral efficacy in the malaria NOD-scid-IL2Rγnull (SCID) mouse model. Structural …

Benzo-ring modification on Malaria Box hit MMV008138: effects on antimalarial potency and microsomal stability

Donna Huber on August 15, 2025

Tetrahydro-β-carboline 1 (MMV008138) controls growth of asexual blood-stage Plasmodium falciparum by inhibiting IspD, an enzyme in the MEP pathway for synthesis of a critical metabolite, isopentenyl pyrophosphate (IPP). We have previously investigated the structure activity relationship (SAR) of three of its four rings (B, C, and D). In this report we investigate the SAR of …

HaloPROTAC3 does not trigger the degradation of the halotagged parasitophorous vacuole membrane protein UIS4 during Plasmodium liver stage development

Donna Huber on May 26, 2025

Targeted protein degradation (TPD) is a novel strategy for developing therapeutics against pathogens. Prior to causing malaria, Plasmodium parasites replicate within hepatocytes as liver stages, surrounded by a parasitophorous vacuole membrane (PVM). We hypothesized that TPD can be employed to trigger host-driven degradation of essential liver stage PVM proteins and lead to parasite death. To …

Discovery and optimization of a novel carboxamide scaffold with selective antimalarial activity

Donna Huber on March 28, 2025

Artemisinin combination therapies (ACTs) are critical components of malaria control worldwide. Alarmingly, ACTs have begun to fail, owing to the rise in artemisinin resistance. Thus, there is an urgent need for an expanded set of novel antimalarials to generate new combination therapies. Herein, we have identified a 1,2,4-triazole-containing carboxamide scaffold that, through scaffold hopping efforts, …

Type I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria

Donna Huber on March 25, 2025

Plasmodium parasites undergo development and replication within hepatocytes before infecting erythrocytes and initiating clinical malaria. Although type I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers …

PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages

Donna Huber on February 7, 2025

Plasmodium species replicate via schizogony, which involves asynchronous nuclear divisions followed by semi-synchronous segmentation and cytokinesis. Successful segmentation requires a double-membranous structure known as the inner membrane complex (IMC). Here we demonstrate that PfFBXO1 (PF3D7_0619700) is critical for both asexual segmentation and gametocyte maturation. In Toxoplasma gondii, the FBXO1 homolog, TgFBXO1, is essential for the …

Screening the Global Health Priority Box against Plasmodium berghei liver stage parasites using an inexpensive luciferase detection protocol

Donna Huber on November 23, 2024

Background: Malaria, a disease caused by parasites of the genus Plasmodium, continues to impact many regions globally. The rise in resistance to artemisinin-based anti-malarial drugs highlights the need for new treatments. Ideally, new anti-malarials will kill the asymptomatic liver stages as well as the symptomatic blood stages. While blood stage screening assays are routine and efficient, …