Related Experiment Video

Updated: Jul 10, 2025

Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
09:13

Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases

Published on: November 22, 2024

1.4K

Antiplasmodial peptaibols act through membrane directed mechanisms

Jennifer E Collins1, Jin Woo Lee2, Frances Rocamora3

  • 1Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826, USA.

Cell Chemical Biology
|November 23, 2023
PubMed

Insights

This study reveals that peptaibols, derived from fungi, target the digestive vacuole in Plasmodium falciparum, offering a novel mechanism against malaria. Resistance arises from mutations in the pfmdr1 gene, suggesting distinct therapeutic pathways.

Area of Science:

  • Medicinal Chemistry
  • Parasitology
  • Molecular Biology

Background:

  • Fungal-derived peptaibols show antiplasmodial activity.
  • Understanding the mechanism of action is crucial for drug development.

Purpose of the Study:

  • To elucidate the antiplasmodial mechanism of action of fungal peptaibols.
  • To investigate resistance mechanisms and stage dependency of potent peptaibols.

Main Methods:

  • Phenotypic assays
  • In vitro resistance evolution studies
  • Transcriptome analysis
  • Ultrastructural analysis
  • Planar membrane reconstitution assays

Main Results:

  • The potent peptaibol HZ NPDG-I disrupts the digestive vacuole (DV) by increasing pH and impairing membrane permeability.
  • HZ NPDG-I forms ion channels and exhibits no cross-resistance with current antimalarial drugs.
  • Resistance to HZ NPDG-I is mediated by mutations in the Plasmodium falciparum multidrug resistance transporter gene (pfmdr1).

Conclusions:

  • Fungal peptaibols represent a promising class of antimalarials with a novel mechanism targeting the parasite's digestive vacuole.
  • PfMDR1 is implicated in resistance to certain peptaibols, indicating potential for drug combination therapies or tailored drug selection.
Keywords:
AMPsAlamethicinMDR1Plasmodiumantiplasmodialdigestive vacuoleion channelmalariapeptaibolpeptides

More Related Videos

Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation08:48

Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation

Published on: January 26, 2016

11.9K
High Yield Purification of Plasmodium falciparum Merozoites For Use in Opsonizing Antibody Assays10:38

High Yield Purification of Plasmodium falciparum Merozoites For Use in Opsonizing Antibody Assays

Published on: July 17, 2014

23.2K

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.6K
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.9K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.3K
Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
534
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.1K
Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
4.5K