Plasmodium 6-cysteine proteins determine the commitment of sporozoites to liver-infection

Plasmodium sporozoites travel a long way from the site where they are released by a mosquito bite to the liver, where they infect hepatocytes and develop into erythrocyte-invasive forms. The success of this infection depends on the ability of the sporozoites to correctly recognize the hepatocyte as a target and change their behavior from migration to infection. However, how this change is accomplished remains incompletely understood. In this paper, we report that 6-cysteine protein family members expressed in sporozoites including B9 are responsible for this ability. Experiments on parasites using double knockouts of B9 and SPECT2, which is essential for sporozoite to migrate through the hepatocyte, showed that the parasites lacked the capacity to stop migration. This finding suggests that interactions between these parasite proteins and hepatocyte-specific cell surface ligands mediate correct recognition of hepatocytes by sporozoites, which is an essential step in malaria transmission to humans. [Display omitted] •B9 is a microneme protein of the Plasmodium sporozoite.•B9-disrupted sporozoites stray into the nucleus of the hepatocyte.•B9 is essential for sporozoites to switch the cell-invasion mode from cell-traversal to productive invasion.•All three 6-cysteine proteins expressed in the sporozoite are essential for this switching.•Plasmodium 6-cysteine proteins determine the commitment of sporozoites to liver infection.