Recent studies highlight that bacterial pathogens can reprogram target cells by influencing epigenetic factors. The type III secretion system (T3SS) is a bacterial nanomachine that resembles a syringe on the bacterial surface. The T3SS ‘needle’ delivers translocon proteins into eukaryotic cell membranes, subsequently allowing injection of bacterial effectors into the cytosol. Here we show that Pseudomonas aeruginosa induces early T3SS-dependent dephosphorylation and deacetylation of histone H3 in eukaryotic cells. This is not triggered by any of the P. aeruginosa T3SS effectors, but results from the insertion of the PopB–PopD translocon into the membrane. This suggests that the P. aeruginosa translocon is a genuine T3SS effector acting as a pore-forming toxin. We visualized the translocon plugged into the host cell membrane after the bacterium has left the site of contact, and demonstrate that subsequent ion exchange through this pore is responsible for histone H3 modifications and host cell subversion.
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The research leading to these results has received funding from the People Programme (Marie Skłodowska-Curie Actions) of the European Union’s Horizon 2020 under REA grant agreement no. 654909. This work was also supported by the French Cystic Fibrosis Foundation (Vaincre la Mucoviscidose RF20140501133), including a postdoctoral fellowship to C.L. We would like to thank L. Allsopp, T. Wood, K. Hui, S. Lory, M. Wolfgang and S. Jin for providing the P. aeruginosa mutants used in this study. We thank M. Ragno, E. Faudry and S. Bouillot (PB&RC Team, CNRS, Grenoble, France) for PopD purification and MAb selection and characterization (financed by the ANR project PRP1.4 T3SS), and I. Attrée for antibody project management and discussions.
The authors declare no competing financial interests.
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Dortet, L., Lombardi, C., Cretin, F. et al. Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome. Nat Microbiol 3, 378–386 (2018). https://doi.org/10.1038/s41564-018-0109-7
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