{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T22:45:45Z","timestamp":1770677145799,"version":"3.49.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Irr and RirA, rather than Fur, serve as the major iron-responsive regulators in the alphaproteobacteria. With only a few exceptions, however, the relative contributions of these transcriptional regulators to the differential expression of specific iron metabolism genes in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>\n            strains are unclear. The gene encoding the outer membrane heme transporter BhuA exhibits maximum expression in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella abortus<\/jats:named-content>\n            2308 during growth under iron-deprived conditions, and mutational studies indicate that this pattern of\n            <jats:italic>bhuA<\/jats:italic>\n            expression is mediated by the iron-responsive regulator Irr. Specifically, a\n            <jats:italic>bhuA-lacZ<\/jats:italic>\n            transcriptional fusion does not produce elevated levels of \u03b2-galactosidase in response to iron deprivation in the isogenic\n            <jats:italic>irr<\/jats:italic>\n            mutant BEA5, and, unlike the parental strain,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>\n            BEA5 cannot utilize heme as an iron source\n            <jats:italic>in vitro<\/jats:italic>\n            and is attenuated in mice. A derivative of the\n            <jats:italic>bhuA-lacZ<\/jats:italic>\n            transcriptional fusion lacking the predicted Irr binding site upstream of the\n            <jats:italic>bhuA<\/jats:italic>\n            promoter does not produce elevated levels of \u03b2-galactosidase in response to iron deprivation in the parental\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>\n            2308 strain, and a direct and specific interaction between a recombinant version of the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>\n            Irr and the\n            <jats:italic>bhuA<\/jats:italic>\n            promoter region was observed in an electrophoretic mobility shift assay. Despite the fact that it lacks the heme regulatory element linked to the iron-responsive degradation of its counterpart in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bradyrhizobium japonicum<\/jats:named-content>\n            , readily detectable levels of Irr were found only in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>\n            2308 cells by Western blot analysis following growth under iron-deprived conditions.\n          <\/jats:p>","DOI":"10.1128\/jb.00372-11","type":"journal-article","created":{"date-parts":[[2011,7,30]],"date-time":"2011-07-30T04:50:36Z","timestamp":1312001436000},"page":"5359-5364","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["The Iron-Responsive Regulator Irr Is Required for Wild-Type Expression of the Gene Encoding the Heme Transporter BhuA in Brucella abortus 2308"],"prefix":"10.1128","volume":"193","author":[{"given":"Eric S.","family":"Anderson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James T.","family":"Paulley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Martinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Gaines","sequence":"additional","affiliation":[{"name":"Present address: OPX Biotechnologies, Inc., Boulder, CO 80301."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendra H.","family":"Steele","sequence":"additional","affiliation":[{"name":"Present address: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40506."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"R. Martin","family":"Roop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1128\/JB.01551-07","article-title":"The AraC-like transcriptional regulator DhbR is required for maximum expression of the 2,3-dihydroxybenzoic acid biosynthesis genes in Brucella abortus 2308 in response to iron deprivation","volume":"190","author":"Anderson E. S.","year":"2007","unstructured":"AndersonE. S. PaulleyJ. T. RoopR. M.II. 2007. The AraC-like transcriptional regulator DhbR is required for maximum expression of the 2,3-dihydroxybenzoic acid biosynthesis genes in Brucella abortus 2308 in response to iron deprivation. J. Bacteriol. 190:1838\u20131842.","journal-title":"J. Bacteriol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.5.2927-2932.2003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.micinf.2007.09.006","article-title":"Nramp1 phagocyte intracellular metal withdrawal defense","volume":"9","author":"Cellier M. F.","year":"2007","unstructured":"CellierM. F. CourvilleP. CampionC.. 2007. Nramp1 phagocyte intracellular metal withdrawal defense. Microbes Infect. 9:1662\u20131670.","journal-title":"Microbes Infect."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.10.4135-4139.1994"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3181\/00379727-89-21914","article-title":"Nutrition of brucellae: utilization of iron, magnesium and manganese for growth","volume":"89","author":"Evenson M. A.","year":"1955","unstructured":"EvensonM. A. GerhardtP.. 1955. Nutrition of brucellae: utilization of iron, magnesium and manganese for growth. Proc. Soc. Exp. Biol. Med. 89:678\u2013680.","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"e_1_3_2_7_2","first-page":"1","volume-title":"Iron and infection. Molecular, physiological and clinical aspects","author":"Griffiths E.","year":"1999","unstructured":"GriffithsE. 1999. Iron in biological systems, p. 1\u201325. In BullenJ. J.GriffithsE. (ed.), Iron and infection. Molecular, physiological and clinical aspects, 2nd ed. John Wiley & Sons, New York, NY.","edition":"2"},{"key":"e_1_3_2_8_2","first-page":"21669","article-title":"The bacterial Irr protein is required for coordination of heme biosynthesis through iron availability","volume":"273","author":"Hamza I.","year":"1998","unstructured":"HamzaI. ChauhanS. HassettR. O'BrianM. R.. 1998. The bacterial Irr protein is required for coordination of heme biosynthesis through iron availability. J. Biochem. 273:21669\u201321674.","journal-title":"J. Biochem."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00584-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.11.4496-4503.1992"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.1099\/mic.0.28213-0","article-title":"Dimeric Brucella abortus Irr protein controls its own expression and binds haem","volume":"151","author":"Mart\u00ednez M.","year":"2005","unstructured":"Mart\u00ednezM. UgaldeR. A. Almir\u00f3nM.. 2005. Dimeric Brucella abortus Irr protein controls its own expression and binds haem. Microbiology 151:3427\u20133433.","journal-title":"Microbiology"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1099\/mic.0.28782-0","article-title":"Irr regulates brucebactin and 2,3-dihydroxybenzoic acid biosynthesis, and is implicated in the oxidative stress resistance and intracellular survival of Brucella abortus","volume":"152","author":"Mart\u00ednez M.","year":"2006","unstructured":"Mart\u00ednezM. UgaldeR. A. Almir\u00f3nM.. 2006. Irr regulates brucebactin and 2,3-dihydroxybenzoic acid biosynthesis, and is implicated in the oxidative stress resistance and intracellular survival of Brucella abortus. Microbiology 152:2591\u20132598.","journal-title":"Microbiology"},{"key":"e_1_3_2_13_2","volume-title":"Experiments in molecular genetics.","author":"Miller J. H.","year":"1972","unstructured":"MillerJ. H. 1972. Experiments in molecular genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY."},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1073\/pnas.022622699","article-title":"Brucella melitensis: a nasty bug with hidden credentials for virulence","volume":"99","author":"Moreno E.","year":"2002","unstructured":"MorenoE. Moriy\u00f3nI.. 2002. Brucella melitensis: a nasty bug with hidden credentials for virulence. Proc. Natl. Acad. Sci. U. S. A. 99:1\u20133.","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization","volume":"306","author":"Nemeth E.","year":"2004","unstructured":"NemethE. . 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090\u20132093.","journal-title":"Science"},{"key":"e_1_3_2_16_2","unstructured":"Reference deleted."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01194-08"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00460-07"},{"key":"e_1_3_2_19_2","unstructured":"PaulleyJ. T. 2007. Ph.D. thesis. East Carolina University Greenville NC."},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"13056","DOI":"10.1073\/pnas.96.23.13056","article-title":"Heme is an effector molecule for iron-dependent degradation of the bacterial iron response regulator (Irr) protein","volume":"96","author":"Qi Z.","year":"1999","unstructured":"QiZ. HamzaI. O'BrianM. R.. 1999. Heme is an effector molecule for iron-dependent degradation of the bacterial iron response regulator (Irr) protein. Proc. Natl. Acad. Sci. U. S. A. 96:13056\u201313061.","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1097-2765(01)00431-2","article-title":"Interaction between the bacterial iron response regulator and ferrochelatase mediates genetic control of heme biosynthesis","volume":"9","author":"Qi Z.","year":"2002","unstructured":"QiZ. O'BrianM. R.. 2002. Interaction between the bacterial iron response regulator and ferrochelatase mediates genetic control of heme biosynthesis. Mol. Cell 9:155\u2013162.","journal-title":"Mol. Cell"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1046\/j.1365-2958.1999.01629.x","article-title":"The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence in mice","volume":"34","author":"Robertson G. T.","year":"1999","unstructured":"RobertsonG. T. RoopR. M.II. 1999. The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence in mice. Mol. Microbiol. 34:690\u2013700.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.12.3482-3489.2000"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00430-009-0123-8","article-title":"Survival of the fittest: how Brucella strains adapt to their intracellular niche in the host","volume":"198","author":"Roop R. M.","year":"2009","unstructured":"RoopR. M.II GainesJ. M. AndersonE. S. CaswellC. C. MartinD. W.. 2009. Survival of the fittest: how Brucella strains adapt to their intracellular niche in the host. Med. Microbiol. Immunol. 198:221\u2013238.","journal-title":"Med. Microbiol. Immunol."},{"key":"e_1_3_2_25_2","volume-title":"Fundamentals of biostatistics","author":"Rosner B.","year":"2000","unstructured":"RosnerB. 2000. Fundamentals of biostatistics, 5th ed. Duxbury, Pacific Grove, CA.","edition":"5"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.2.733-744.2006"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"16023","DOI":"10.1074\/jbc.M109.067215","article-title":"Heme-responsive DNA binding by the global iron regulator Irr from Bradyrhizobium leguminosarum","volume":"285","author":"Singleton C.","year":"2010","unstructured":"SingletonC. . 2010. Heme-responsive DNA binding by the global iron regulator Irr from Bradyrhizobium leguminosarum. J. Biol. Chem. 285:16023\u201316031.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01571-08"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10534-008-9192-1","article-title":"Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria","volume":"22","author":"Small S. K.","year":"2009","unstructured":"SmallS. K. PuriS. O'BrianM. R.. 2009. Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria. Biometals 22:89\u201397.","journal-title":"Biometals"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.2.417-425.1991"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1099\/00221287-148-12-4059","article-title":"RirA, an iron-responsive regulator in the symbiotic bacterium Rhizobium leguminosarum","volume":"148","author":"Todd J. D.","year":"2002","unstructured":"ToddJ. D. . 2002. RirA, an iron-responsive regulator in the symbiotic bacterium Rhizobium leguminosarum. Microbiology 148:4059\u20134071.","journal-title":"Microbiology"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s00438-006-0115-y","article-title":"The Rhizobium leguminosarum regulator IrrA affects the transcription of a wide range of genes in response to Fe availability","volume":"275","author":"Todd J. D.","year":"2006","unstructured":"ToddJ. D. SawersG. RodionovD. A. JohnstonA. W. B.. 2006. The Rhizobium leguminosarum regulator IrrA affects the transcription of a wide range of genes in response to Fe availability. Mol. Genet. Genomics 275:564\u2013577.","journal-title":"Mol. Genet. Genomics"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.66.1.82-91.1953"},{"key":"e_1_3_2_34_2","first-page":"79","volume-title":"Virulence mechanisms of bacterial pathogens.","author":"Weinberg E. D.","year":"1995","unstructured":"WeinbergE. D. 1995. Acquisition of iron and other nutrients in vivo, p. 79\u201393. In RothJ. A. BolinC. A. BrogdenK. A. MinionF. C. WannemuehlerM. J. (ed.), Virulence mechanisms of bacterial pathogens. ASM Press, Washington, DC."},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.beha.2004.09.001","article-title":"Modification of iron regulation by the inflammatory response","volume":"18","author":"Weiss G.","year":"2005","unstructured":"WeissG. 2005. Modification of iron regulation by the inflammatory response. Best Pract. Res. Clin. Haematol. 18:183\u2013201.","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1365-2958.2006.05101.x","article-title":"Bradyrhizobium japonicum senses iron through the status of haem to regulate iron homeostasis and metabolism","volume":"60","author":"Yang J.","year":"2006","unstructured":"YangJ. . 2006. Bradyrhizobium japonicum senses iron through the status of haem to regulate iron homeostasis and metabolism. Mol. Microbiol. 60:427\u2013437.","journal-title":"Mol. Microbiol."}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00372-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00372-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T17:20:40Z","timestamp":1627579240000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.00372-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10]]},"references-count":35,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2011,10]]}},"alternative-id":["10.1128\/JB.00372-11"],"URL":"https:\/\/doi.org\/10.1128\/jb.00372-11","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10]]},"assertion":[{"value":"2011-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-07-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-09-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}