title: A global investigation of the Bacillus subtilis iron-sparing response identifies major changes in metabolism.
abstract: The Bacillus subtilis ferric uptake regulator (Fur) protein is the major sensor of cellular iron status. When iron is limiting for growth, derepression of the Fur regulon increases the cellular capacity for iron uptake and mobilizes an iron-sparing response mediated in large part by a small noncoding RNA named FsrA. FsrA functions, in collaboration with three small basic proteins (FbpABC), to repress many "low-priority" iron-containing enzymes. We have used transcriptome analyses to gain insights into the scope of the iron-sparing response and to define subsets of genes dependent for their repression on FsrA, FbpAB, and/or FbpC. Enzymes of the tricarboxylic acid (TCA) cycle, including aconitase and succinate dehydrogenase (SDH), are major targets of FsrA-mediated repression, and as a consequence, flux through this pathway is significantly decreased in a fur mutant. FsrA also represses the DctP dicarboxylate permease and the iron-sulfur-containing enzyme glutamate synthase (GltAB), which serves as a central link between carbon and nitrogen metabolism. Allele-specific suppression analysis was used to document a direct RNA-RNA interaction between the FsrA small RNA (sRNA) and the gltAB leader region. We further demonstrated that distinct regions of FsrA are required for the translational repression of the GltAB and SDH enzyme complexes.
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, New York, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Smaldone
authors.forename: Olga
authors.initials: O
authors.lastname: Revelles
authors.forename: Ahmed
authors.initials: A
authors.lastname: Gaballa
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.forename: Haike
authors.initials: H
authors.lastname: Antelmann
authors.forename: John D
authors.initials: JD
authors.lastname: Helmann
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002952:Citric Acid Cycle / Q000502:physiology; D019295:Computational Biology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D007501:Iron / Q000378:metabolism*; D009154:Mutation; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D009876:Operon; D012329:RNA, Bacterial; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron