title: ExsB is required for correct assembly of the Pseudomonas aeruginosa type III secretion apparatus in the bacterial membrane and full virulence in vivo.
abstract: Pseudomonas aeruginosa is responsible for high-morbidity infections of cystic fibrosis patients and is a major agent of nosocomial infections. One of its most potent virulence factors is a type III secretion system (T3SS) that injects toxins directly into the host cell cytoplasm. ExsB, a lipoprotein localized in the bacterial outer membrane, is one of the components of this machinery, of which the function remained elusive until now. The localization of the exsB gene within the exsCEBA regulatory gene operon suggested an implication in the T3SS regulation, while its similarity with yscW from Yersinia spp. argued in favor of a role in machinery assembly. The present work shows that ExsB is necessary for full in vivo virulence of P. aeruginosa. Furthermore, the requirement of ExsB for optimal T3SS assembly and activity is demonstrated using eukaryotic cell infection and in vitro assays. In particular, ExsB promotes the assembly of the T3SS secretin in the bacterial outer membrane, highlighting the molecular role of ExsB as a pilotin. This involvement in the regulation of the T3S apparatus assembly may explain the localization of the ExsB-encoding gene within the regulatory gene operon.
authors.affiliation: Université Grenoble Alpes, Bacterial Pathogenesis and Cellular Responses Group, Grenoble, France CEA, iRTSV, Grenoble, France CNRS, ERL5261, Grenoble, France INSERM, U1036_S Biology of Cancer and Infection Laboratory, Grenoble, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Perdu
authors.affiliation: Université Grenoble Alpes, Bacterial Pathogenesis and Cellular Responses Group, Grenoble, France CEA, iRTSV, Grenoble, France CNRS, ERL5261, Grenoble, France INSERM, U1036_S Biology of Cancer and Infection Laboratory, Grenoble, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Huber
authors.affiliation: Université Grenoble Alpes, Bacterial Pathogenesis and Cellular Responses Group, Grenoble, France CEA, iRTSV, Grenoble, France CNRS, ERL5261, Grenoble, France INSERM, U1036_S Biology of Cancer and Infection Laboratory, Grenoble, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bouillot
authors.affiliation: Schools of Cellular & Molecular Medicine and Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Ariel
authors.initials: A
authors.lastname: Blocker
authors.affiliation: Université Grenoble Alpes, Bacterial Pathogenesis and Cellular Responses Group, Grenoble, France CEA, iRTSV, Grenoble, France CNRS, ERL5261, Grenoble, France INSERM, U1036_S Biology of Cancer and Infection Laboratory, Grenoble, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Elsen
authors.affiliation: Université Grenoble Alpes, Bacterial Pathogenesis and Cellular Responses Group, Grenoble, France CEA, iRTSV, Grenoble, France CNRS, ERL5261, Grenoble, France INSERM, U1036_S Biology of Cancer and Infection Laboratory, Grenoble, France.
authors.forename: Ina
authors.initials: I
authors.lastname: Attrée
authors.affiliation: Université Grenoble Alpes, Bacterial Pathogenesis and Cellular Responses Group, Grenoble, France CEA, iRTSV, Grenoble, France CNRS, ERL5261, Grenoble, France INSERM, U1036_S Biology of Cancer and Infection Laboratory, Grenoble, France eric.faudry@cea.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Faudry
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000382:microbiology; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D055503:Protein Multimerization; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000502:physiology*; D016019:Survival Analysis; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C095022:ExsB protein, Pseudomonas aeruginosa; D008074:Lipoproteins; D008565:Membrane Proteins; D037521:Virulence Factors