Open AccessModulation of host cell SUMOylation facilitates efficient development of Plasmodium berghei and Toxoplasma gondii
Author(s) -
Maruthi Mulaka,
Singh Dipti,
Reddy Segireddy Rameswara,
Mastan Babu S.,
Mishra Satish,
Kumar Kota Arun
Publication year - 2017
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12723
Subject(s) - biology , plasmodium berghei , sumo protein , toxoplasma gondii , host (biology) , virology , plasmodium (life cycle) , microbiology and biotechnology , genetics , immunology , malaria , parasite hosting , gene , ubiquitin , computer science , world wide web , antibody
Summary 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.