Coordination of transcriptional and translational regulations in human cells infected by Listeria monocytogenes

The invasion of mammalian cells by intracellular bacterial pathogens reshuffles their gene expression and functions; however, we lack dynamic insight into the distinct control levels that shape the host response. By comparing ribosome profiling and transcriptome data, we have addressed the respective contribution of transcriptional and translational regulations during a time-course of infection of human intestinal epithelial cells by an epidemic strain of Listeria monocytogenes. Upregulations were dominated by early transcriptional activation of pro-inflammatory genes, whereas translation inhibition appeared as the major source of downregulations. Instead of a widespread shutoff, translation inhibition affected durably and specifically transcripts encoding components of the translation machinery, and harbouring a 59-terminal oligopyrimidine motif. Pre-silencing the most repressed target gene (PABPC1) slowed down the intracellular multiplication of Listeria, suggesting that the infected host cell can benefit from the repression of genes involved in protein synthesis and thereby better control infection.