title: Treponema pallidum Lipoprotein TP0435 Expressed in Borrelia burgdorferi Produces Multiple Surface/Periplasmic Isoforms and mediates Adherence.
abstract: The ability of Treponema pallidum, the syphilis spirochete to colonize various tissues requires the presence of surface-exposed adhesins that have been difficult to identify due to the inability to culture and genetically manipulate T. pallidum. Using a Borrelia burgdorferi-based heterologous system and gain-in-function approach, we show for the first time that a highly immunogenic lipoprotein TP0435 can be differentially processed into multiple isoforms with one variant stochastically displayed on the spirochete surface. TP0435 was previously believed to be exclusively located in T. pallidum periplasm. Furthermore, non-adherent B. burgdorferi strain expressing TP0435 acquires the ability to bind to a variety of host cells including placental cells and exhibits slow opsonophagocytosis in vitro similar to poor ex vivo phagocytosis of T. pallidum by host macrophages reported previously. This phenomenon of production of both surface and periplasmic immunogenic lipoprotein isoforms has possible implications in immune evasion of the obligate pathogen T. pallidum during infection.
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Kamfai
authors.initials: K
authors.lastname: Chan
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Thayer
authors.initials: T
authors.lastname: Nasereddin
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Alter
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Centurion-Lara
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98104, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Giacani
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Nikhat
authors.initials: N
authors.lastname: Parveen
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D019897:Periplasm / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000235:genetics / Q000276:immunology; D014210:Treponema pallidum / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D020033:Protein Isoforms; C496546:Tp32 protein, Treponema pallidum