Sumoylation controls host anti‐bacterial response to the gut invasive pathogen Shigella flexneri

Autor: Alexandra Andrieux, Filip Golebiowski, Sabrina Fritah, Philippe J. Sansonetti, Ronald T. Hay, Joëlle Mounier, Nouara Lhocine, Anne Dejean, Grégory Jouvion
Přispěvatelé: Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe labellisée Ligue contre le Cancer, Centre de Recherche Public de la Santé, Pathogénie Microbienne Moléculaire, University of Dundee, Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], This work was supported by grants from LNCC (Equipe labellisée), Odyssey-RE, INCa, ANR and ERC. S.F. was supported by RUBICON and Sidaction., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Cheriet Rauline, Samia
Jazyk: angličtina
Rok vydání: 2014
Předmět:
MESH: Inflammation
MESH: Shigella flexneri
[SDV]Life Sciences [q-bio]
SUMO protein
Haploinsufficiency
medicine.disease_cause
Biochemistry
Shigella flexneri
Mice
0302 clinical medicine
Ubc9
Shigella
MESH: Animals
Pathogen
0303 health sciences
biology
MESH: Sumoylation
Intestinal epithelium
Intestines
[SDV] Life Sciences [q-bio]
MESH: Epithelial Cells
Host-Pathogen Interactions
Small Ubiquitin-Related Modifier Proteins
MESH: Haploinsufficiency
medicine.symptom
transcription
MESH: Intestines
Shigellosis
MESH: Dysentery
Bacillary
Inflammation
Microbiology
03 medical and health sciences
proteomics
Genetics
medicine
Animals
Humans
Molecular Biology
MESH: Mice
030304 developmental biology
Dysentery
Bacillary
Intestinal permeability
MESH: Humans
Scientific Reports
MESH: Host-Pathogen Interactions
Sumoylation
Epithelial Cells
medicine.disease
biology.organism_classification
MESH: Small Ubiquitin-Related Modifier Proteins
SUMO
inflammation
MESH: Protein Processing
Post-Translational
Protein Processing
Post-Translational
030217 neurology & neurosurgery
Zdroj: EMBO Reports
EMBO Reports, EMBO Press, 2014, 15 (9), pp.965-972. ⟨10.15252/embr.201338386⟩
EMBO Reports, 2014, 15 (9), pp.965-972. ⟨10.15252/embr.201338386⟩
Europe PubMed Central
EMBO reports
ISSN: 1469-221X
1469-3178
DOI: 10.15252/embr.201338386⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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