Article Shigella flexneri targets the HP1c subcode through the phosphothreonine lyase OspF

HP1 proteins are transcriptional regulators that, like histones, are targets for post-translational modifications defining an HP1-mediated subcode. HP1c has multiple phosphorylation sites, including serine 83 (S83) that marks it to sites of active transcription. In a guinea pig model for Shigella enterocolitis, we observed that the defective type III secretion mxiD Shigella flexneri strain caused more HP1c phosphorylation in the colon than the wild-type strain. Shigella interferes with HP1 phosphorylation by injecting the phospholyase OspF. This effector interacts with HP1c and alters its phosphorylation at S83 by inactivating ERK and consequently MSK1, a downstream kinase. MSK1 that here arises as a novel HP1c kinase, phosphorylates HP1c at S83 in the context of an MSK1-HP1c complex, and thereby favors its accumulation on its target genes. Genome-wide transcriptome analysis reveals that this mechanism is linked to up-regulation of proliferative gene and fine-tuning of immune gene expression. Thus, in addition to histones, bacteria control host transcription by modulating the activity of HP1 proteins, with potential implications in transcrip-tional reprogramming at the mucosal barrier