title: DnaK from Bifidobacterium animalis subsp. lactis is a surface-exposed human plasminogen receptor upregulated in response to bile salts.
abstract: Bifidobacterium animalis subsp. lactis lives in the gastrointestinal tract of most mammals, including humans. Recently, for the probiotic strain B. animalis subsp. lactis BI07, a dose-dependent plasminogen-binding activity was demonstrated and five putative plasminogen-binding proteins were identified. Here we investigated the role of surface DnaK as a B. animalis subsp. lactis BI07 plasminogen receptor. DnaK was visualized on the bacterial cell surface by transmission electron microscopy. The His-tagged recombinant DnaK protein showed a high affinity for human plasminogen, with an equilibrium dissociation constant in the nanomolar range. The capability to tolerate physiological concentrations of bile salts is a crucial feature for an intestinal symbiont micro-organism. By proteome analysis we demonstrated that the long-term exposure of B. animalis subsp. lactis BI07 to bile salts results in the upregulation of important surface plasminogen receptors such as DnaK and enolase. Moreover, adaptation of B. animalis subsp. lactis BI07 to physiological concentrations of bile salts significantly increased its capacity to interact with the host plasminogen system. By enhancing the bacterial capacity to interact with the host plasminogen, the gut bile environment may facilitate the colonization of the human host by B. animalis subsp. lactis BI07.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Candela
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Centanni
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Fiori
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Biagi
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Turroni
authors.affiliation: Department of Pathological Anatomy Martinelli, S. Orsola-Malpighi, University of Bologna, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Orrico
authors.affiliation: Department of Microbial Pathogenicity, Helmholtz Centre for Infection Research GmbH, Braunschweig, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
authors.affiliation: Department of Genetics of Microorganisms, Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Brigidi
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis / Q000378:metabolism*; D001644:Bifidobacterium / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D020543:Proteome / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D018840:HSP70 Heat-Shock Proteins; D020543:Proteome; D011994:Recombinant Proteins; D010958:Plasminogen; D010751:Phosphopyruvate Hydratase