title: The Bordetella Secreted Regulator BspR Is Translocated into the Nucleus of Host Cells via Its N-Terminal Moiety: Evaluation of Bacterial Effector Translocation by the Escherichia coli Type III Secretion System.
abstract: Bordetella bronchiseptica is genetically related to B. pertussis and B. parapertussis, which cause respiratory tract infections in humans. These pathogens possess a large number of virulence factors, including the type III secretion system (T3SS), which is required for the delivery of effectors into the host cells. In a previous study, we identified a transcriptional regulator, BspR, that is involved in the regulation of the T3SS-related genes in response to iron-starved conditions. A unique feature of BspR is that this regulator is secreted into the extracellular milieu via the T3SS. To further characterize the role of BspR in extracellular localization, we constructed various truncated derivatives of BspR and investigated their translocation into the host cells using conventional translocation assays. In this study, the effector translocation was evaluated by the T3SS of enteropathogenic E. coli (EPEC), since the exogenous expression of BspR triggers severe repression of the Bordetella T3SS expression. The results of the translocation assays using the EPEC T3SS showed that the N-terminal 150 amino acid (aa) residues of BspR are sufficient for translocation into the host cells in a T3SS-dependent manner. In addition, exogenous expression of BspR in HeLa cells demonstrated that the N-terminal 100 aa residues are involved in the nuclear localization. In contrast, the N-terminal 54 aa residues are sufficient for the extracellular secretion into the bacterial culture supernatant via the EPEC T3SS. Thus, BspR is not only a transcriptional regulator in bacteria cytosol, but also functions as an effector that translocates into the nuclei of infected host cells.
authors.affiliation: Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Abe
authors.affiliation: Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Nishimura
authors.affiliation: Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kurushima
authors.affiliation: Laboratory of Bacterial Infection, Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Asaomi
authors.initials: A
authors.lastname: Kuwae
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016950:Bordetella bronchiseptica / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D019556:COS Cells; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000069296:Type III Secretion Systems / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D000069296:Type III Secretion Systems; D037521:Virulence Factors