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Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur.<jats:italic>L. interrogans<\/jats:italic>encodes four predicted Fur homologs; we have constructed a mutation in one of these,<jats:italic>la1857<\/jats:italic>. We conducted microarray analysis to identify iron-responsive genes and to study the effects of<jats:italic>la1857<\/jats:italic>mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte<jats:italic>L. biflexa<\/jats:italic>and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of<jats:italic>la1857<\/jats:italic>, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the<jats:italic>la1857<\/jats:italic>mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.<\/jats:p>","DOI":"10.1128\/iai.00435-10","type":"journal-article","created":{"date-parts":[[2010,8,31]],"date-time":"2010-08-31T01:12:35Z","timestamp":1283217155000},"page":"4850-4859","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":87,"title":["Transcriptional Response of<i>Leptospira interrogans<\/i>to Iron Limitation and Characterization of a PerR Homolog"],"prefix":"10.1128","volume":"78","author":[{"given":"Miranda","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald L.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen Ai","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Haake","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095"},{"name":"Division of Infectious Diseases, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Zuerner","sequence":"additional","affiliation":[{"name":"Infectious Bacterial Diseases Research Unit, National Animal Disease Center, USDA Agricultural Research Service, Ames, Iowa 50010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Adler","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia"},{"name":"Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics"},{"name":"Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2009.03.012"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.14.3.703-708.1976"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.16.4742-4747.1995"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-6445(03)00055-X"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002030050600"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00324-07"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00460-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00830-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.19.3.785-791.1978"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.11.6387-6390.1989"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00921.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/3.6.1127"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.10.4759-4764.1987"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.17.5428-5437.1993"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.10.3484"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00989-08"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.5.2311-2318.2002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000463"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04030.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.03227.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.9.5117-5126.1989"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr9004597"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-20-2-246"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.21.6348-6357.2003"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.22.5815-5821.1998"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1046\/j.1365-2958.2003.03589.x","volume":"49","year":"2003","unstructured":"Guegan, R., J. 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