Cysteine cathepsin proteases in apicomplexan parasites

Cysteine cathepsins are papain-like proteases which play key roles in a large range of organisms, including apicomplexan parasites. These obligate endoparasites are responsible for many devastating diseases in human and/or animal hosts, for which available treatments are limited or face the emergence of resistance. This review presents the cysteine cathepsins expressed by five major Apicomplexa (Plasmodium falciparum, Cryptosporidium parvum, Toxoplasma gondii, Eimeria tenella and Babesia bovis), highlighting available data on their structures, specific or common features, and biological functions in the parasite biology and host-parasite interactions. Although they belong to the same phylum, apicomplexan parasites have very distinct life cycles and biology, which are well adapted to the hosts they infect and to the tissues within which they develop. Accordingly, apicomplexan cysteine cathepsins display a wide variety of functions, associated with shared (e.g., invasion of and egress from host cells) or unique (e.g., degradation of haemoglobin in P. falciparum) biological pathways. Through their crucial functions and involvement in multiple parasite stages, these parasitic proteases represent assumed therapeutic targets. The description of apicomplexan cysteine cathepsins also appears uneven within the phylum, and further exploration of their biology and role is needed to drive novel preventive or curative intervention strategies.