title: A type III secretion negative clinical strain of Pseudomonas aeruginosa employs a two-partner secreted exolysin to induce hemorrhagic pneumonia.
abstract: Virulence of Pseudomonas aeruginosa is typically attributed to its type III secretion system (T3SS). A taxonomic outlier, the P. aeruginosa PA7 strain, lacks a T3SS locus, and no virulence phenotype is attributed to PA7. We characterized a PA7-related, T3SS-negative P. aeruginosa strain, CLJ1, isolated from a patient with fatal hemorrhagic pneumonia. CLJ1 is highly virulent in mice, leading to lung hemorrhage and septicemia. CLJ1-infected primary endothelial cells display characteristics of membrane damage and permeabilization. Proteomic analysis of CLJ1 culture supernatants identified a hemolysin/hemagglutinin family pore-forming toxin, Exolysin (ExlA), that is exported via ExlB, representing a putative two-partner secretion system. A recombinant P. aeruginosa PAO1ΔpscD::exlBA strain, deficient for T3SS but engineered to express ExlA, gained lytic capacity on endothelial cells and full virulence in mice, demonstrating that ExlA is necessary and sufficient for pathogenicity. This highlights clinically relevant T3SS-independent hypervirulence, isolates, and points to a broader P. aeruginosa pathogenic repertoire.
authors: Biologie du Cancer et de l'Infection (UMR-S1036) and Biologie à Grande Echelle (UMR1038), INSERM, Grenoble 38054, France; Bacterial Pathogenicity and Cellular Responses, Centre National de la Recherche Scientifique (CNRS), Grenoble 38054, France; University Joseph Fourier-Grenoble I, Grenoble F-38042, France; CEA, iRTSV, Grenoble 38054, France.
authors: Sylvie
authors: S
authors: Elsen
authors: Biologie du Cancer et de l'Infection (UMR-S1036) and Biologie à Grande Echelle (UMR1038), INSERM, Grenoble 38054, France; Bacterial Pathogenicity and Cellular Responses, Centre National de la Recherche Scientifique (CNRS), Grenoble 38054, France; University Joseph Fourier-Grenoble I, Grenoble F-38042, France; CEA, iRTSV, Grenoble 38054, France.
authors: Philippe
authors: P
authors: Huber
authors: Biologie du Cancer et de l'Infection (UMR-S1036) and Biologie à Grande Echelle (UMR1038), INSERM, Grenoble 38054, France; Bacterial Pathogenicity and Cellular Responses, Centre National de la Recherche Scientifique (CNRS), Grenoble 38054, France; University Joseph Fourier-Grenoble I, Grenoble F-38042, France; CEA, iRTSV, Grenoble 38054, France.
authors: Stéphanie
authors: S
authors: Bouillot
authors: Biologie du Cancer et de l'Infection (UMR-S1036) and Biologie à Grande Echelle (UMR1038), INSERM, Grenoble 38054, France; University Joseph Fourier-Grenoble I, Grenoble F-38042, France; CEA, iRTSV, Grenoble 38054, France.
authors: Yohann
authors: Y
authors: Couté
authors: University Joseph Fourier-Grenoble I, Grenoble F-38042, France; Laboratoire de Bactériologie-Hygiène Hospitalière, CHU de Grenoble, Grenoble 38043, France; CNRS, UMR 5163, Laboratoire Adaptation et Pathogénie des Microorganismes, Grenoble 38042, France.
authors: Pierre
authors: P
authors: Fournier
authors: Medical Intensive Care Unit, Albert Michallon University Hospital, Grenoble 38000, France.
authors: Yohann
authors: Y
authors: Dubois
authors: University Joseph Fourier-Grenoble I, Grenoble F-38042, France; Medical Intensive Care Unit, Albert Michallon University Hospital, Grenoble 38000, France; University Paris Diderot (Paris VII), Medical ICU, Bichat University Hospital, Paris 75018, France.
authors: Jean-François
authors: JF
authors: Timsit
authors: University Joseph Fourier-Grenoble I, Grenoble F-38042, France; Laboratoire de Bactériologie-Hygiène Hospitalière, CHU de Grenoble, Grenoble 38043, France; CNRS, UMR 5163, Laboratoire Adaptation et Pathogénie des Microorganismes, Grenoble 38042, France.
authors: Max
authors: M
authors: Maurin
authors: Biologie du Cancer et de l'Infection (UMR-S1036) and Biologie à Grande Echelle (UMR1038), INSERM, Grenoble 38054, France; Bacterial Pathogenicity and Cellular Responses, Centre National de la Recherche Scientifique (CNRS), Grenoble 38054, France; University Joseph Fourier-Grenoble I, Grenoble F-38042, France; CEA, iRTSV, Grenoble 38054, France. Electronic address: ina.attree-delic@cea.fr.
authors: Ina
authors: I
authors: Attrée
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000382:microbiology / Q000502:physiology; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D008168:Lung / Q000473:pathology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins; D026901:Membrane Transport Proteins; D052899:Pore Forming Cytotoxic Proteins; D037521:Virulence Factors