title: Sumoylation controls host anti-bacterial response to the gut invasive pathogen Shigella flexneri.
abstract: Shigella flexneri, the etiological agent of bacillary dysentery, invades the human colonic epithelium and causes its massive inflammatory destruction. Little is known about the post-translational modifications implicated in regulating the host defense pathway against Shigella. Here, we show that SUMO-2 impairs Shigella invasion of epithelial cells in vitro. Using mice haploinsufficient for the SUMO E2 enzyme, we found that sumoylation regulates intestinal permeability and is required to restrict epithelial invasion and control mucosal inflammation. Quantitative proteomics reveals that Shigella infection alters the sumoylation status of a restricted set of transcriptional regulators involved in intestinal functions and inflammation. Consistent with this, sumoylation restricts the pro-inflammatory transcriptional response of Shigella-infected guts. Altogether, our results show that the SUMO pathway is an essential component of host innate protection, as it reduces the efficiency of two key steps of shigellosis: invasion and inflammatory destruction of the intestinal epithelium.
authors.affiliation: Laboratory of Nuclear Organization and Oncogenesis, Institut Pasteur, Paris, France INSERM U993, Paris, France Equipe Labellisée Ligue Nationale Contre le Cancer, Paris, France NorLux Neuro-Oncology Laboratory, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg, Luxembourg.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fritah
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France INSERM U786, Paris, France.
authors.forename: Nouara
authors.initials: N
authors.lastname: Lhocine
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences University of Dundee, Dundee, UK.
authors.forename: Filip
authors.initials: F
authors.lastname: Golebiowski
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France INSERM U786, Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Mounier
authors.affiliation: Laboratory of Nuclear Organization and Oncogenesis, Institut Pasteur, Paris, France INSERM U993, Paris, France Equipe Labellisée Ligue Nationale Contre le Cancer, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Andrieux
authors.affiliation: Unité d'Histopathologie Humaine et Modèles Animaux, Institut Pasteur, Paris, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Jouvion
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences University of Dundee, Dundee, UK.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France INSERM U786, Paris, France philippe.sansonetti@pasteur.fr anne.dejean@pasteur.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sansonetti
authors.affiliation: Laboratory of Nuclear Organization and Oncogenesis, Institut Pasteur, Paris, France INSERM U993, Paris, France Equipe Labellisée Ligue Nationale Contre le Cancer, Paris, France philippe.sansonetti@pasteur.fr anne.dejean@pasteur.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
mesh_terms: D000818:Animals; D004405:Dysentery, Bacillary / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D057895:Haploinsufficiency / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012763:Shigella flexneri / Q000378:metabolism / Q000472:pathogenicity; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation / Q000235:genetics*
chemical_list: C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins
keywords: SUMO; Shigella flexneri; Ubc9; inflammation; proteomics; transcription
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