title: Irr regulates brucebactin and 2,3-dihydroxybenzoic acid biosynthesis, and is implicated in the oxidative stress resistance and intracellular survival of Brucella abortus.
abstract: Brucella abortus faces iron deprivation in both nature and the host. To overcome this limitation, Brucella secretes the siderophores 2,3-dihydroxybenzoic acid and brucebactin. A Fur-like protein named Irr has previously been characterized in B. abortus; this protein is present in the alpha-2 group of Proteobacteria only, where it negatively regulates haem biosynthesis when iron is scarce. Additional evidence that Irr also regulates the synthesis of both siderophores is presented here. Transcriptional lacZ fusion and chemical determinations revealed that Irr induced the transcription of the operon involved in the synthesis of the catecholic siderophores, which were consequently secreted under conditions of iron limitation. Irr was able to bind the upstream region of the operon, as shown by electrophoretic mobility shift assay. A B. abortus irr mutant showed higher intracellular haem content, catalase activity and resistance to hydrogen peroxide than the wild-type strain. The mutation also improved the replication and survival of iron-depleted bacteria within cultured mammalian cells. Although the pathogenesis of Brucella correlates with its ability to replicate intracellularly, pathogenicity was not attenuated when assayed in a murine model.
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Instituto Tecnológico de Chascomús (IIB, INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de General San Martín (CONICET-UNSAM), San Martín 1650, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Instituto Tecnológico de Chascomús (IIB, INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de General San Martín (CONICET-UNSAM), San Martín 1650, Argentina.
authors.forename: Rodolfo A
authors.initials: RA
authors.lastname: Ugalde
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Instituto Tecnológico de Chascomús (IIB, INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de General San Martín (CONICET-UNSAM), San Martín 1650, Argentina.
authors.forename: Marta
authors.initials: M
authors.lastname: Almirón
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002003:Brucella abortus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism*; D018384:Oxidative Stress; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D017262:Siderophores / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D062385:Hydroxybenzoates; D017262:Siderophores; C009135:2,3-dihydroxybenzoic acid; D011972:Receptor, Insulin; C066542:insulin receptor-related receptor