Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome.
Laurent DortetCharlotte LombardiFrançois CretinAndréa DessenAlain FillouxPublished in: Nature microbiology (2018)
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.
Keyphrases
- type iii
- pseudomonas aeruginosa
- induced apoptosis
- cell cycle arrest
- single cell
- dna methylation
- cystic fibrosis
- cell therapy
- escherichia coli
- ultrasound guided
- biofilm formation
- gene expression
- signaling pathway
- endoplasmic reticulum stress
- bone marrow
- drug resistant
- immune response
- mesenchymal stem cells
- staphylococcus aureus
- antimicrobial resistance
- oxidative stress