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Abstract
Plasmodium falciparum, the causative agent of malaria, has a class of genes from prokaryotic origins, known as the Clp family of chaperones and proteases. Several of them, including the protease PfClpP, localize to a unique metabolic organelle in the parasite known as the apicoplast. Little is known about apicoplast biology, but it has been shown that drugs targeting this non-photosynthetic plastid are clinically effective. Our data show that the PfClpP protease is essential for asexual growth, and that it forms a proteolytic complex with other Clp proteins to regulate apicoplast biogenesis and homeostasis. We have generated a conditional knockdown mutant of PfClpP that enables us to reduce protein levels of PfClpP by over 95%. Using these conditional mutants as a tool, we screen for small molecules that act as specific PfClpP inhibitors with the hypothesis that specific inhibitors will exhibit differential effects depending on cellular levels of PfClpP.