title: VirJ Is a Brucella Virulence Factor Involved in the Secretion of Type IV Secreted Substrates.
abstract: The VirB secretion apparatus in Brucella belongs to the type IV secretion systems present in many pathogenic bacteria and is absolutely necessary for the efficient evasion of the Brucella-containing vacuole from the phagocytic route in professional phagocytes. This system is responsible for the secretion of a plethora of effector proteins that alter the biology of the host cell and promote the intracellular replication process. Although many VirB substrates have been identified in Brucella, we still know very little about the secretion mechanism that mediates their translocation across the two membranes and the periplasmic space. In this manuscript, we describe the identification of a gene, virJ, that codes for a protein with periplasmic localization that is involved in the intracellular replication process and virulence in mice. Our analysis revealed that this protein is necessary for the secretion of at least two VirB substrates that have a periplasmic intermediate and that it directly interacts with them. We additionally show that VirJ also associates with the apparatus per se and that its absence affects the assembly of the complex. We hypothesize that VirJ is part of a secretion platform composed of the translocon and several secretion substrates and that it probably coordinates the proper assembly of this macromolecular complex.
authors.affiliation: From the Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde", Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina.
authors.forename: Mariela Giselda
authors.initials: MG
authors.lastname: Del Giudice
authors.affiliation: From the Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde", Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina.
authors.forename: Peter Hans
authors.initials: PH
authors.lastname: Döhmer
authors.affiliation: From the Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde", Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Spera
authors.affiliation: From the Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde", Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina.
authors.forename: Fernando Tomás
authors.initials: FT
authors.lastname: Laporte
authors.affiliation: From the Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde", Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina.
authors.forename: María Inés
authors.initials: MI
authors.lastname: Marchesini
authors.affiliation: From the Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde", Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina czibener@iibintech.com.ar.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Czibener
authors.affiliation: From the Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde", Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina jugalde@iibintech.com.ar.
authors.forename: Juan Esteban
authors.initials: JE
authors.lastname: Ugalde
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002003:Brucella abortus / Q000472:pathogenicity; D002006:Brucellosis / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000821:virology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D019897:Periplasm / Q000378:metabolism*; D011485:Protein Binding; D000069319:Type IV Secretion Systems / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D000069319:Type IV Secretion Systems; D037521:Virulence Factors
keywords: Brucella; host-pathogen interaction; intracellular trafficking; microbial pathogenesis; protein secretion; virulence factor