Proteases are thought to be potentially useful targets for developing medicines to control filariasis caused by parasitic nematodes. To screen cysteine proteases essential for viability of nematodes, fifteen cathepsin B/L-like genes of
Caenorhabditis elegans, as a model of the parasitic nematodes, were interfered by RNAi. As a result, ∼100% embryonic lethality was observed only when
Ce-cpl-1, encoding a cathepsin L-like protease, was knocked down. Subsequent attempts were made to identify the orthologs of
Ce-cpl-1 in the parasitic nematode
Brugia malayi by molecular cloning and sequencing of some EST clones. The sequences of five distinct open reading frames were identified, all of which are most homologous to
Ce-CPL-1 in
C.
elegans. The consensus catalytic triad of cathepsin L-like proteases is conserved among four of the five predicted proteins. Phylogenetic analysis suggests that one of them,
Bm-CPL-1, is closely related to the proteases from other filarial parasites. However, neither
Bm-CPL-1 nor the other four predicted proteins belong to the same sub-branch of
Ce-CPL-1 in the phylogenetic tree. In
B.
malayi, the functions of
Ce-CPL-1 are presumably shared by some of the predicted proteases including
Bm-CPL-1, although the possibility cannot be ruled out that
B.
malayi has an unknown cysteine protease more resembling
Ce-CPL-1.
View full abstract