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

• Published in: EMBO reports 2014-09, Vol.15 (9), p.965-972
• Main Authors: Fritah, Sabrina, Lhocine, Nouara, Golebiowski, Filip, Mounier, Joëlle, Andrieux, Alexandra, Jouvion, Grégory, Hay, Ronald T, Sansonetti, Philippe, Dejean, Anne
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Bacteriology; Dysentery; Dysentery, Bacillary; Dysentery, Bacillary - genetics; Dysentery, Bacillary - metabolism; Dysentery, Bacillary - microbiology; EMBO23; EMBO31; Epithelial Cells; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelial Cells - pathology; Genes; Haploinsufficiency; Haploinsufficiency - genetics; Host-Pathogen Interactions; Host-Pathogen Interactions - genetics; Humans; Immune response; Infections; Inflammation; Inflammation - metabolism; Inflammation - microbiology; Inflammation - pathology; Intestines; Intestines - microbiology; Intestines - pathology; Life Sciences; Mice; Pathology; Permeability; Protein Processing, Post-Translational; Protein Processing, Post-Translational - genetics; proteomics; Scientific Report; Scientific Reports; Shigella flexneri; Shigella flexneri - metabolism; Shigella flexneri - pathogenicity; Small Ubiquitin-Related Modifier Proteins; Small Ubiquitin-Related Modifier Proteins - genetics; Small Ubiquitin-Related Modifier Proteins - metabolism; SUMO; Sumoylation; Sumoylation - genetics; transcription; Ubc9; Waterborne diseases
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201338386

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. Synopsis This study shows that the SUMO pathway is essential in the host response to Shigella invasion by regulating the interplay between intestinal permeability and transcriptional immune response. It is the first report of a role of SUMO in infection by Gram‐negative bacteria SUMO regulates Shigella epithelial invasion both in vitro and in vivo Shigella infection decreases sumoylation of transcriptional regulators Graphical Abstract This study shows that the SUMO pathway is essential in the host response to Shigella invasion by regulating the interplay between intestinal permeability and transcriptional immune response.