Format

Send to

Choose Destination
Cell Microbiol. 2009 Jan;11(1):95-105. doi: 10.1111/j.1462-5822.2008.01242.x. Epub 2008 Oct 22.

Irreversible effect of cysteine protease inhibitors on the release of malaria parasites from infected erythrocytes.

Author information

1
Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

By studying the inactivation of malaria parasite culture by cysteine protease inhibition using confocal microscopy of living cells and electron microscopy of high-pressure frozen and freeze-substituted cells, we report the precise step in the release of malaria parasites from erythrocytes that is likely regulated by cysteine proteases: the opening of the erythrocyte membrane, liberating parasites for the next round of infection. Inhibition of cysteine proteases within the last few minutes of cycle does not affect rupture of the parasitophorus vacuole but irreversibly blocks the subsequent rupture of the host cell membrane, locking in resident parasites, which die within a few hours of captivity. This irreversible inactivation of mature parasites inside host cells makes plasmodial cysteine proteases attractive targets for antimalarials, as parasite-specific cysteine protease inhibitors may significantly augment multi-target drug cocktails.

PMID:
19016793
PMCID:
PMC2883916
DOI:
10.1111/j.1462-5822.2008.01242.x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center