Work

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

Year: 2008

Type: article

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.

Source: Cellular Microbiology

DOI: 10.1111/j.1462-5822.2008.01242.x

Authors: Svetlana Glushakova, Julia Mazar, Martin F. Hohmann-Marriott, Erinn Hama, Joshua Zimmerberg

Institutions: National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Biomedical Imaging and Bioengineering

Language: English

Topic: Malaria Research and Control

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: National Institutes of Health