Scientific Publications
Computational prediction and experimental validation of Salmonella Typhimurium SopE-mediated fine-tuning of autophagy in intestinal epithelial cells
Frontiers in Cellular & Infection Microbiology
Macroautophagy is a ubiquitous homeostasis and health-promoting recycling process of eukaryotic cells, targeting misfolded proteins, organelles and intracellular infectious agents. Some intracellular pathogens such as Salmonella enterica serovar Typhimurium hijack this process during pathogenesis. Here we investigate potential protein-protein interactions between host transcription factors and secreted effector proteins of Salmonella and their effect on host gene transcription. A systems-level analysis identified a network of Salmonella effector proteins that had the potential to affect autophagy-related genes. The effect of a SPI-1 effector protein, SopE, that was predicted to interact with proteins of the autophagy process, was investigated to validate our approach. We revealed that SopE might have a double role in the modulation of autophagy. Following initial increase of MAP1LC3B transcription triggered by Salmonella infection, subsequent decrease in MAP1LC3B transcription at 6h post-infection was SopE-dependent. SopE also played a role in modulation of the autophagy flux machinery, in particular MAP1LC3B and p62 autophagy proteins, depending on the level of autophagy already taking place. Upon typical infection of epithelial cells, the autophagic flux is increased. However, when autophagy was chemically induced prior to infection, SopE dampened the autophagic flux. The same was also observed when most of the intracellular Salmonella cells were not associated with the SCV (strain lacking sifA) regardless of the autophagy induction status before infection. We demonstrated how regulatory network analysis can be used to better characterise the impact of pathogenic effector proteins, in this case, Salmonella. Such interdisciplinary studies can increase our understanding of the infection process and point out targets important in intestinal epithelial cell defence.
Frontiers in Cellular & Infection Microbiology
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