A SUBTILISIN-LIKE PROTEIN IN SECRETORY ORGANELLES OF PLASMODIUM-FALCIPARUM MEROZOITES

In the vertebrate host, the malaria parasite invades and replicates as exually within circulating erythrocytes. Parasite proteolytic enzymes play an essential but poorly understood role in erythrocyte invasion. We have identified a Plasmodium falciparum gene, denoted pf-sub-1, enc oding a member of the subtilisin-like serine protease family (subtilas es). The pfsub-1 gene is ex pressed in asexual blood stages of P. falc iparum, and the primary gene product (PfSUB-1) undergoes post-translat ional processing during secretory transport in a manner consistent wit h its being converted to a mature, enzymatically active form, as docum ented for other subtilases. In the invasive merozoite, the putative ma ture protease (p47) is concentrated in dense granules, which are secre tory organelles located toward the apical end of the merozoite. At som e point following merozoite release and completion of erythrocyte inva sion, p47 is secreted from the parasite in a truncated, soluble form. The subcellular location and timing of secretion of p47 suggest that i t is likely to play a role in erythrocyte invasion. PfSUB-1 is a new p otential target for antimalarial drug development.