title: Modulation of host cell SUMOylation facilitates efficient development of Plasmodium berghei and Toxoplasma gondii.
abstract: 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 invade mammalian 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 during Toxoplasma infection. We provide a hitherto unknown mechanism of regulating host gene expression by Apicomplexan parasites through altering host SUMOylation.
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Mulaka
authors.initials: M
authors.lastname: Maruthi
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Dipti
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Segireddy Rameswara
authors.initials: SR
authors.lastname: Reddy
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Babu S
authors.initials: BS
authors.lastname: Mastan
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Kota Arun
authors.initials: KA
authors.lastname: Kumar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D025842:SUMO-1 Protein / Q000096:biosynthesis*; D051901:Smad4 Protein / Q000378:metabolism; D034101:Sporozoites / Q000166:cytology; D058207:Sumoylation / Q000502:physiology*; D014122:Toxoplasma / Q000235:genetics* / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: Plasmodium EEFs; SMAD4; SUMO1; Toxoplasma; conjugation enzyme E2; host SUMOylation