Vesicular mechanisms of drug resistance in apicomplexan parasites

SUMMARY Vesicular mechanisms of drug resistance are known to exist across prokaryotes and eukaryotes. Vesicles are sacs that form when a lipid bilayer 'bends' to engulf and isolate contents from the cytoplasm or extracellular environment. They have a wide range of functions, including vehicles of communication within and across cells, trafficking of protein intermediates to their rightful organellar destinations, and carriers of substrates destined for autophagy. This review will provide an in-depth understanding of vesicular mechanisms of apicomplexan parasites, Plasmodium and Toxoplasma (that respectively cause malaria and toxoplasmosis). It will integrate mechanistic and evolutionarily insights gained from these and other pathogenic eukaryotes to develop a new model for plasmodial resistance to artemisinins, a class of drugs that have been the backbone of modern campaigns to eliminate malaria worldwide. We also discuss extracellular vesicles that present major vesicular mechanisms of drug resistance in parasite protozoa (that apicomplexans are part of). Finally, we provide a broader context of clinical drug resistance mechanisms of Plasmodium, Toxoplasma, as well as Cryptosporidium and Babesia, that are prominent members of the phyla, causative agents of cryptosporidiosis and babesiosis and significant for human and animal health.