ArticleGut microbes2017
Shigella depends on SepA to destabilize the intestinal epithelial integrity via cofilin activation.
Article in Gut microbes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
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- KLF7 enhances the inflammatory response in LPS-induced alveolar epithelial cellsCentral-European journal of immunology · 2025Article
- SPATEs promote the survival ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Genomic Dissection of an EnteroaggregativeInternational journal of molecular sciences · 2024Article
- Epithelial Cell Infection Analyses with Shigella.Journal of visualized experiments : JoVE · 2024Article
- Plasmid-encoded toxin ofFrontiers in cellular and infection microbiology · 2024Article
- Coactosin-like protein 1 regulates integrity and repair of model intestinal epithelial barriers via actin binding dependent and independent mechanisms.Frontiers in cell and developmental biology · 2024Article
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- A foundational approach to culture and analyze malnourished organoids.Gut microbes · 2023Article
- Recent Advances in Cell-Based In Vitro Models to Recreate Human Intestinal Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs.International journal of molecular sciences · 2023Article
- Impact of enteric bacterial infections at and beyond the epithelial barrier.Nature reviews. Microbiology · 2023Review
- Crystal structure of a subtilisin-like autotransporter passenger domain reveals insights into its cytotoxic function.Nature communications · 2023Article
- Structural and biophysical characterization of the secreted, β-helical adhesin EtpA of Enterotoxigenic Escherichia coli.PloS one · 2023Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Shigella is unique among enteric pathogens, as it invades colonic epithelia through the basolateral pole. Therefore, it has evolved the ability to breach the intestinal epithelial barrier to deploy an arsenal of effector proteins, which permits bacterial invasion and leads to a severe inflammatory response. However, the mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To address this question, we used both an intestinal polarized model and a human ex-vivo model to further characterize the early events of host-bacteria interactions. Our results showed that secreted Serine Protease A (SepA), which belongs to the serine protease autotransporter of Enterobacteriaceae family, is responsible for critically disrupting the intestinal epithelial barrier. Such disruption facilitates bacterial transit to the basolateral pole of the epithelium, ultimately fostering the hallmarks of the disease pathology. SepA was found to cause a decrease in active LIM Kinase 1 (LIMK1) levels, a negative inhibitor of actin-remodeling proteins, namely cofilin. Correspondingly, we observed increased activation of cofilin, a major actin-polymerization factor known to control opening of tight junctions at the epithelial barrier. Furthermore, we resolved the crystal structure of SepA to elucidate its role on actin-dynamics and barrier disruption. The serine protease activity of SepA was found to be required for the regulatory effects on LIMK1 and cofilin, resulting in the disruption of the epithelial barrier during infection. Altogether, we demonstrate that SepA is indispensable for barrier disruption, ultimately facilitating Shigella transit to the basolateral pole where it effectively invades the epithelium.
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