title: IdeR is required for iron homeostasis and virulence in Mycobacterium tuberculosis.
abstract: Iron is an essential but potentially harmful nutrient, poorly soluble in aerobic conditions, and not freely available in the human host. To acquire iron, bacteria have evolved high affinity iron acquisition systems that are expressed under iron limitation often in conjunction with virulence determinants. Because excess iron can be dangerous, intracellular iron must be tightly controlled. In mycobacteria, IdeR functions as a global iron dependent transcriptional regulator, but because inactivation of ideR is lethal for Mycobacterium tuberculosis, it has not been possible to use genetics to fully characterize this protein's function or examine the requirement of iron regulation during tuberculosis infection. In this work, a conditional M. tuberculosis ideR mutant was generated and used to study the basis of IdeR's essentiality. This investigation uncovered positive regulation of iron storage as a critical aspect of IdeR's function in regular culture and a prominent factor for survival under stresses associated with life in macrophages. Moreover, this study demonstrates that IdeR is indispensable in the mouse model of tuberculosis, thereby linking iron homeostasis to virulence in M. tuberculosis.
authors.affiliation: Public Health Research Institute at New Jersey Medical School, Rutgers State University of New Jersey, 225 Warren Street, Newark, NJ, 07103, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Pandey
authors.forename: G Marcela
authors.initials: GM
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D018384:Oxidative Stress / Q000235:genetics; D026361:Reactive Nitrogen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014376:Tuberculosis / Q000382:microbiology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C096348:IdeR protein, Mycobacterium tuberculosis; D026361:Reactive Nitrogen Species; D012097:Repressor Proteins; D037521:Virulence Factors; D007501:Iron