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multiple plasmepsin knockout mutants lacking plasmepsins I-III and I-IV, respectively show a significant increased parasite susceptibility to cyteine protease inhibitors. A ninefold increase in the potency of the calpain inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) against parasites lacking all four plasmepsins (I-IV) is observed. It is hypothesized that plasmepsins and some cysteine proteases play redundant or complementary roles in the digestive vacuole and that the absence of all plasmepsins (I-IV) renders these parasites highly susceptible to N-acetyl-leucinyl-leucinyl-norleucinal-mediated inhibition of falcipains
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