Computational prediction and experimental validation of Salmonella Typhimurium SopE-mediated fine-tuning of autophagy in intestinal epithelial cells

• DOI: 10.3389/fcimb.2022.834895
• Publication Date: 2022-08-17T07:03:38Z
• Authors: Amanda Demeter; Anne-Claire Jacomin; Lejla Gul; Ashleigh Lister; James Lipscombe; Rachele Invernizzi; Priscilla Branchu; Iain Macaulay; Ioannis P. Nezis; Robert A. Kingsley; Tamas Korcsmaros; Isabelle Hautefort
• Keywords: Salmonella enterica; Transcription

Macroautophagy is a ubiquitous homeostasis and health-promoting recycling process of eukaryotic cells, targeting misfolded proteins, damaged organelles intracellular infectious agents. Some pathogens such as Salmonella enterica serovar Typhimurium hijack this during pathogenesis. Here we investigate potential protein-protein interactions between host transcription factors secreted effector proteins their effect on gene transcription. A systems-level analysis identified that had the to affect core autophagy regulation. The SPI-1 protein, SopE, was predicted interact with regulatory process, investigated validate our approach. We then confirmed experimentally SopE can directly bind SP1, factor, which modulates expression MAP1LC3B . also revealed might have double role in modulation autophagy: Following initial increase triggered by infection, subsequent decrease at 6h post-infection SopE-dependent. played flux machinery, particular p62 depending level already taking place. Upon typical infection epithelial autophagic increased. However, when chemically induced prior dampened flux. same observed most cells were not associated SCV (strain lacking sifA ) regardless induction status before infection. demonstrated how network be used better characterise impact pathogenic case, This study complements previous work specific pathogen effectors through direct interaction proteins. show influence upstream regulation process. Such interdisciplinary studies understanding point out targets important intestinal cell defense.