The Proteases and Pathogenicity of Parasitic Protozoa

Abstract

Protozoan parasites are among the most prevalent pathogens worldwide. Diseases like malaria, leishmaniasis, amebiasis, and trypanosomiasis affect hundreds of millions of people. Recent advances in our understanding of the biochemistry and molecular biology of these organisms has focused attention on specific parasite molecules that are key to the parasite life cycle or the pathogenesis of the diseases they produce. One group of enzymes that plays myriad roles in these processes are the parasite-derived proteases. Different types of proteases are frequently expressed at different stages of the parasite life cycle to support parasite replication and metamorphosis. Intracellular parasites such as those that produce malaria and Chagas' disease express high levels of protease activity to efficiently degrade host proteins like hemoglobin. In other instances, such as infection with Entamoeba histolytica, the causative agent of amebiasis, proteases released by the parasite can damage host cells and tissues, contributing to host tissue damage and parasite invasion. Detailed studies of these enzymes have led to model systems for the study of parasite gene regulation, parasite metabolism, and the host-parasite interplay. In some instances, proteases appear to be promising targets for the development of new antiparasitic chemotherapy.

Inhibition of cathepsin B by its propeptide: Use of overlapping peptides to identify a critical segment

“…The results obtained here using overlapping peptides spanning the cysteine proteinase proregion agree with those reported from crystal structures of human and rat procathepsin B [13,14]. This promising approach to designing more selective inhibitors of cysteine proteinases will be extended to the proregions of other papain-like proteinases, especially those of protozoan parasites like trypanosomes, that are involved in both spreading and host infection [30,31], but have no specific substrate or inhibitors that can selectively control their activity.…”

Overexpression of Leucyl Aminopeptidase in Plasmodium falciparum Parasites

“…During the development and asexual reproduction of malaria parasites within erythrocytes, as much as 65-75% of erythrocyte hemoglobin is internalized and digested (1,2). There is still some conjecture as to the reason why the parasite needs to degrade such a large proportion of the erythrocyte hemoglobin, but several theories have been proposed (3,4).…”

Functional Analysis of Cathepsin B-like Cysteine Proteases fromLeishmania donovani Complex

“…Leishmania parasites contain high levels of cysteine proteases, belonging to cathepsin L and cathepsin B families (4). Cysteine proteases have been shown to play critical roles in the pathogenesis of parasitic protozoan infections (5). Studies using CA074, a cathepsin B-specific inhibitor-treated BALB/c mice, showed resistance against Leishmania major infection and also showed the shift of immune responses from Th2 to protective Th1 type (6).…”