Cysteine proteases during larval migration and development of helminths in their final host

Abstract

Neglected tropical diseases caused by metazoan parasites are major public health concerns, and therefore, new methods for their control and elimination are needed. Research over the last 25 years has revealed the vital contribution of cysteine proteases to invasion of and migration by (larval) helminth parasites through host tissues, in addition to their roles in embryogenesis, molting, egg hatching, and yolk degradation. Their central function to maintaining parasite survival in the host has made them prime intervention targets for novel drugs and vaccines. This review focuses on those helminth cysteine proteases that have been functionally characterized during the varied early stages of development in the human host and embryogenesis.

Fig 1. Expression patterns of genes encoding cysteine proteases and their inhibitors over the life cycle of O. volvulus and B. malayi.

A. Expression of CPL-like, CPZ-like, and CPB-like proteases and their inhibitors over the lifecycle of O. volvulus. Gene expression in reads per kilobase of transcript per million mapped reads (RPKMs) is z-score normalized and then used to cluster genes based on expression [43]. B. Expression of CPL-like, CPZ-like, and CPB-like proteases and their inhibitors over the lifecycle of B. malayi. Gene expression in fragments per kilobase of transcript per million mapped reads (FPKMs) is z-score normalized and then used to cluster genes based on expression [45]. As these data were collected as part of 2 independent studies, the units of normalization differ, as do some of the sampled stages. CPL, cathepsin L; CPZ, cathepsin Z; CPB, cathepsin B.