Fluorescent tagging of Plasmodium circumsporozoite protein allows imaging of sporozoite formation but blocks egress from oocysts

Abstract

The circumsporozoite protein, CSP is the major surface protein of Plasmodium sporozoites, the form of malaria parasites transmitted by mosquitoes. CSP is involved in sporozoite formation within and egress from oocysts, entry into mosquito salivary glands and mammalian liver as well as migration in the skin. Antibodies against CSP can stop infection prior to the first round of parasite replication in the liver. CSP consists of different domains and is proteolytically cleaved prior to hepatocyte invasion. Part of CSP has been developed into a licensed vaccine against malaria. Yet, how CSP facilitates sporozoite formation, oocyst egress and hepatocyte specific invasion is still not fully understood. Here, we generated a series of parasites expressing full-length versions of CSP as fusion proteins with the green fluorescent protein. This enabled the investigation of sporozoite formation in living oocysts and revealed a dominant negative function of some GFP-CSP fusions during sporozoite egress.