Open AccessIrreversible effect of cysteine protease inhibitors on the release of malaria parasites from infected erythrocytes
Author(s) -
Glushakova Svetlana,
Mazar Julia,
HohmannMarriott Martin F.,
Hama Erinn,
Zimmerberg Joshua
Publication year - 2009
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2008.01242.x
Subject(s) - proteases , cysteine protease , biology , cysteine , protease , parasite hosting , vacuole , cysteine proteinase inhibitors , malaria , biochemistry , microbiology and biotechnology , protease inhibitor (pharmacology) , plasmodium falciparum , virology , enzyme , immunology , programmed cell death , caspase , virus , apoptosis , cytoplasm , world wide web , computer science , antiretroviral therapy , viral load
Summary 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.