Pore-forming activity of the $Pseudomonas\ aeruginosa$ type III secretion system translocon alters the host epigenome

Autor: Charlotte Lombardi, Alain Filloux, Laurent Dortet, François Cretin, Andréa Dessen
Přispěvatelé: AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), MRC Centre for Molecular Microbiology and Infection, Department of Life Sciences, Imperial College London, London, United Kingdom, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse bactérienne et réponses cellulaires (PBRC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Brazilian Biosciences National Laboratory (LNBio), National Center for Research in Energy and Materials, Vaincre la Mucoviscidose RF20140501133, ANR project PRP1.4 T3SS, European Project: 654909,H2020,H2020-MSCA-IF-2014,T6SS-PSEUDO-LIP(2016), Université Grenoble Alpes, Inserm, CEA, BIG-Biologie du Cancer et de l’Infection, Grenoble, France, Imperial College London, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Medical Research Council (MRC)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
EFFECTOR TARGETS
NF-KAPPA-B
Moths
medicine.disease_cause
Applied Microbiology and Biotechnology
Virulence factor
Epigenesis
Genetic
Type three secretion system
Histones
INFECTION
Type III Secretion Systems
MESH: Animals
MESH: Epigenesis
Genetic
PHOSPHORYLATION
MESH: Bacterial Proteins
Host cell membrane
MESH: Histones
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Effector
Chemistry
MESH: Moths
EPITHELIAL-CELLS
Translocon
Cell biology
Histone Code
Larva
Host-Pathogen Interactions
Pseudomonas aeruginosa
MESH: Pseudomonas aeruginosa
Life Sciences & Biomedicine
Microbiology (medical)
GENES
Immunology
Microbiology
03 medical and health sciences
MESH: Type III Secretion Systems
Bacterial Proteins
Genetics
medicine
Animals
Humans
Secretion
HISTONE H3
PROTEIN PHOSPHATASES
Antigens
Bacterial
Science & Technology
MESH: Humans
Cell Membrane
MESH: Host-Pathogen Interactions
Cell Biology
Epigenome
biochemical phenomena
metabolism
and nutrition
MAPK
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
030104 developmental biology
MESH: Histone Code
A549 Cells
MESH: HeLa Cells
bacteria
MESH: A549 Cells
VI SECRETION
MESH: Larva
MESH: Antigens
Bacterial
HeLa Cells
MESH: Cell Membrane
Zdroj: Nature Microbiology
Nature Microbiology, Nature Publishing Group, 2018, 3, pp.378-386. ⟨10.1038/s41564-018-0109-7⟩
Nature Microbiology, Nature Publishing Group, 2018, 3 (3), pp.378-386. ⟨10.1038/s41564-018-0109-7⟩
Nature Microbiology, 2018, 3, pp.378-386. ⟨10.1038/s41564-018-0109-7⟩
Nature Microbiology, 2018, 3 (3), pp.378-386. ⟨10.1038/s41564-018-0109-7⟩
ISSN: 2058-5276
DOI: 10.1038/s41564-018-0109-7⟩
Popis: 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. The pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon serves as a virulence factor to induce host epigenome modification and promote infection.
Databáze: OpenAIRE
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