title: Salmonella Engages Host MicroRNAs To Modulate SUMOylation: a New Arsenal for Intracellular Survival.
abstract: Posttranslational modifications (PTMs) can alter many fundamental properties of a protein. One or combinations of them have been known to regulate the dynamics of many cellular pathways and consequently regulate all vital processes. Understandably, pathogens have evolved sophisticated strategies to subvert these mechanisms to achieve instantaneous control over host functions. Here, we present the first report of modulation by intestinal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) of host SUMOylation, a PTM pathway central to all fundamental cellular processes. Both in cell culture and in a mouse model, we observed that S. Typhimurium infection led to a dynamic SUMO-conjugated proteome alteration. The intracellular survival of S. Typhimurium was dependent on SUMO status as revealed by reduced infection and Salmonella-induced filaments (SIFs) in SUMO-upregulated cells. S. Typhimurium-dependent SUMO modulation was seen as a result of depletion of crucial SUMO pathway enzymes Ubc-9 and PIAS1, at both the protein and the transcript levels. Mechanistically, depletion of Ubc-9 relied on upregulation of small noncoding RNAs miR30c and miR30e during S. Typhimurium infection. This was necessary and sufficient for both down-modulation of Ubc-9 and a successful infection. Thus, we demonstrate a novel strategy of pathogen-mediated perturbation of host SUMOylation, an integral mechanism underlying S. Typhimurium infection and intracellular survival.
authors.affiliation: Regional Centre for Biotechnology, Faridabad, India.
authors.forename: Smriti
authors.initials: S
authors.lastname: Verma
authors.affiliation: Regional Centre for Biotechnology, Faridabad, India Manipal University, Karnataka, India.
authors.forename: Gayatree
authors.initials: G
authors.lastname: Mohapatra
authors.affiliation: Regional Centre for Biotechnology, Faridabad, India Manipal University, Karnataka, India.
authors.forename: Salman Mustfa
authors.initials: SM
authors.lastname: Ahmad
authors.affiliation: Regional Centre for Biotechnology, Faridabad, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Rana
authors.affiliation: Regional Centre for Biotechnology, Faridabad, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Jain
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Jasneet Kaur
authors.initials: JK
authors.lastname: Khalsa
authors.affiliation: Regional Centre for Biotechnology, Faridabad, India cvsrikanth@rcb.res.in.
authors.forename: C V
authors.initials: CV
authors.lastname: Srikanth
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D012480:Salmonella Infections / Q000473:pathology; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D058207:Sumoylation / Q000235:genetics*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9