SUMOylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport and protein-protein interactions. Several viruses and bacteria modulate host SUMOylation machinery for efficient infection. Plasmodium sporozoites are infective forms of malaria parasite that infect hepatocytes and transforms into exoerythrocytic forms (EEFs). Here we show that, during EEF development, the distribution of SUMOylated proteins in host cell nuclei was significantly reduced and expression of the SUMOylation enzymes was downregulated. Plasmodium EEFs destabilized the host cytoplasmic protein SMAD4 by inhibiting its SUMOylation. SUMO1 overexpression was detrimental to EEF growth and insufficiency of the only conjugating enzyme Ubc9/E2 promoted EEF growth. The expression of genes involved in suppression of host cell defense pathways during infection was reversed during SUMO1 overexpression, as revealed by transcriptomic analysis. The inhibition of host cell SUMOylation was also observed in Toxoplasma. We provide a hitherto unknown mechanism of regulating host gene expression through altering host SUMOylation by Apicomplexan parasites.

SUMOylation is a reversible post translational modification of proteins that regulates protein stabilization, nucleocytoplasmic transport and protein-protein interactions. Several viruses and bacteria modulate host SUMOylation machinery for efficient infection. Plasmodium sporozoites are infective forms of malaria parasite that infect hepatocytes and transforms into exoerythrocytic forms (EEFs). Here we show that, during EEF development, the distribution of SUMOylated proteins in host cell nuclei was significantly reduced and expression of the SUMOylation enzymes was downregulated. Plasmodium EEFs destabilized the host cytoplasmic protein SMAD4 by inhibiting its SUMOylation. SUMO1 overexpression was detrimental to EEF growth and insufficiency of the only conjugating enzyme Ubc9/E2 promoted EEF growth. The expression of genes involved in suppression of host cell defense pathways during infection was reversed during SUMO1 overexpression, as revealed by transcriptomic analysis. The inhibition of host cell SUMOylation was also observed in Toxoplasma. We provide a hitherto unknown mechanism of regulating host gene expression through altering host SUMOylation by Apicomplexan parasites.