Cellular Microbiology · Published 2026-01-01 · DOI 10.1155/cmi/5623652
Plasmodium infects hepatocytes prior to establishing a pathogenic blood stage infection. During liver stage development, parasites modulate their host cells to survive, grow, and multiply, resulting in the formation of merozoites that are released into the blood stream. Compared with the number of parasite proteins that are exported into the erythrocyte, evidence exists for the export of only a very few parasite proteins into the host hepatocyte. Here, we screened multiple Plasmodium berghei candidate proteins for liver stage expression and export into the hepatocyte. To ascertain expression and export, proteins were tagged with either mCherry or 3xcMyc. This screening resulted in the identification of a novel liver stage exported protein, that is, LSEP. Although LSEP fused to mCherry failed to translocate into the hepatocyte, cMyc-tagged LSEP was exported into the hepatocyte cytosol, indicating that the tag structure or size influences export into the hepatocyte. In addition, the known liver stage–specific and exported protein LISP2 was tagged with mCherry/cMyc in multiple locations (N-terminal, internal, and C-terminal). Notably, only LISP2 tagged with cMyc at its N-terminus translocated into the hepatocyte, showing that both the choice of the tag and the location of the tag are important for identifying proteins that are exported into the hepatocyte cytosol. Identifying novel exported proteins may, in turn, lead to the identification of potential targets for possible therapeutics.
Abstract from DOAJ. Public domain (CC0 1.0).
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