Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells

Autoren

Christoph Gelhaus
Radim Vicik
Tanja Schirmeister
Matthias Leippe

DOI

10.1515/bc.2005.059

eISSN

1437-4315

ISSN

1431-6730

Ausgabe der Veröffentlichung

5

Zeitschrift

Biological Chemistry

Datum der Veröffentlichung

2005

Status

Published

Herausgeber

Walter de Gruyter GmbH

Herausgeber URL

http://dx.doi.org/10.1515/bc.2005.059

Datum der Datenerfassung

2024

Titel

Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells

Ausgabe der Zeitschrift

386

Datenquelle: Crossref

Abstract

The malaria parasite Plasmodium falciparum invades human red blood cells. Before infecting new erythrocytes, the merozoites have to exit their host cell to get into the blood plasma. Knowledge about the mechanism of egress is scarce, but it is thought that proteases are basically involved in this step. We have introduced a biotinylated dibenzyl aziridine-2,3-dicarboxylate (bADA) as an irreversible cysteine protease inhibitor to study the mechanism of merozoite release and to identify the proteases involved. The compound acts on parasite proteins in the digestive vacuole and in the host cell cytosol, as judged by fluorescence microscopy. The inhibitor blocks rupture of the host cell membrane, leading to clustered merozoite structures, as evidenced by immunoelectron microscopy. Interestingly, bADA did not prevent rupture of the parasitophorous vacuole membrane (PVM) that surrounds the parasite during the period of intraerythrocytic maturation. The compound appears to be a valuable template for the development of inhibitors specific for individual plasmodial proteases, which would be useful tools to dissect the molecular mechanisms underlying the process of merozoite release and consequently to develop potent antimalarial drugs.

Addresses

Zoologisches Institut der Universität Kiel, Olshausenstr. 40, D-24098 Kiel, Germany.

Autoren

Christoph Gelhaus
Radim Vicik
Tanja Schirmeister
Matthias Leippe

DOI

10.1515/bc.2005.059

eISSN

1437-4315

Externe Identifier

PubMed Identifier: 15927894

Open access

false

ISSN

1431-6730

Ausgabe der Veröffentlichung

5

Zeitschrift

Biological chemistry

Schlüsselwörter

Erythrocytes
Erythrocyte Membrane
Animals
Humans
Plasmodium falciparum
Aziridines
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors
Affinity Labels
Microscopy, Immunoelectron
Microscopy, Fluorescence
In Vitro Techniques

Sprache

eng

Medium

Print

Paginierung

499 - 502

Datum der Veröffentlichung

2005

Status

Published

Datum der Datenerfassung

2005

Titel

Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

386

Datenquelle: Europe PubMed Central

Abstract

The malaria parasite Plasmodium falciparum invades human red blood cells. Before infecting new erythrocytes, the merozoites have to exit their host cell to get into the blood plasma. Knowledge about the mechanism of egress is scarce, but it is thought that proteases are basically involved in this step. We have introduced a biotinylated dibenzyl aziridine-2,3-dicarboxylate (bADA) as an irreversible cysteine protease inhibitor to study the mechanism of merozoite release and to identify the proteases involved. The compound acts on parasite proteins in the digestive vacuole and in the host cell cytosol, as judged by fluorescence microscopy. The inhibitor blocks rupture of the host cell membrane, leading to clustered merozoite structures, as evidenced by immunoelectron microscopy. Interestingly, bADA did not prevent rupture of the parasitophorous vacuole membrane (PVM) that surrounds the parasite during the period of intraerythrocytic maturation. The compound appears to be a valuable template for the development of inhibitors specific for individual plasmodial proteases, which would be useful tools to dissect the molecular mechanisms underlying the process of merozoite release and consequently to develop potent antimalarial drugs.

Autoren

Christoph Gelhaus
Radim Vicik
Tanja Schirmeister
Matthias Leippe

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/15927894

DOI

10.1515/BC.2005.059

ISSN

1431-6730

Ausgabe der Veröffentlichung

5

Zeitschrift

Biol Chem

Schlüsselwörter

Affinity Labels
Animals
Aziridines
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors
Erythrocyte Membrane
Erythrocytes
Humans
In Vitro Techniques
Microscopy, Fluorescence
Microscopy, Immunoelectron
Plasmodium falciparum

Sprache

eng

Country

Germany

Paginierung

499 - 502

Datum der Veröffentlichung

2005

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2005

Titel

Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

386

Datenquelle: PubMed

Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells

Werkzeuge