title: Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering β-catenin degradation.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-κB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of β-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell-cell contacts and reduced expression of the β-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce β-catenin degradation, which then represses processes that are directly linked to tissue recovery.
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors: Catherine
authors: C
authors: Cott
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors: Roland
authors: R
authors: Thuenauer
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors: Alessia
authors: A
authors: Landi
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors: Katja
authors: K
authors: Kühn
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University Freiburg, Albertstraße 19, 79104 Freiburg, Germany.
authors: Samuel
authors: S
authors: Juillot
authors: Centre de Recherches sur les Macromolécules Végétales, UPR5301 CNRS and University of Grenoble Alpes, BP53, 38041 Grenoble cédex 09, France.
authors: Anne
authors: A
authors: Imberty
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors: Josef
authors: J
authors: Madl
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors: Thorsten
authors: T
authors: Eierhoff
authors: Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University Freiburg, Albertstraße 19, 79104 Freiburg, Germany. Electronic address: winfried.roemer@bioss.uni-freiburg.de.
authors: Winfried
authors: W
authors: Römer
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000494:pharmacology*; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000494:pharmacology*; D018613:Microscopy, Confocal; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015853:Cysteine Proteinase Inhibitors; D019012:Integrin beta1; C534600:LecB protein, Pseudomonas aeruginosa; D037102:Lectins; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D051176:beta Catenin; C067713:lactacystin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine
keywords: Acute lung injury; Bacterial pathogenesis; Migration; NF-κB; Proliferation; Wnt