title: The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins.
abstract: Regulation of bacterial iron homeostasis is often controlled by the iron-sensing ferric uptake repressor (Fur). The Bacillus subtilis Fur protein acts as an iron-dependent repressor for siderophore biosynthesis and iron transport proteins. Here, we demonstrate that Fur also coordinates an iron-sparing response that acts to repress the expression of iron-rich proteins when iron is limiting. When Fur is inactive, numerous iron-containing proteins are down-regulated, including succinate dehydrogenase, aconitase, cytochromes, and biosynthetic enzymes for heme, cysteine, and branched chain amino acids. As a result, a fur mutant grows slowly in a variety of nutrient conditions. Depending on the growth medium, rapid growth can be restored by mutations in one or more of the molecular effectors of the iron-sparing response. These effectors include the products of three Fur-regulated operons that encode a small RNA (FsrA) and three small, basic proteins (FbpA, FbpB, and FbpC). Extensive complementarity between FsrA and the leader region of the succinate dehydrogenase operon is consistent with an RNA-mediated translational repression mechanism for this target. Thus, iron deprivation in B. subtilis activates pathways to remodel the proteome to preserve iron for the most critical cellular functions.
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, NY 14853-8101, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Gaballa
authors.forename: Haike
authors.initials: H
authors.lastname: Antelmann
authors.forename: Claudio
authors.initials: C
authors.lastname: Aguilar
authors.forename: Sukhjit K
authors.initials: SK
authors.lastname: Khakh
authors.forename: Kyung-Bok
authors.initials: KB
authors.lastname: Song
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Smaldone
authors.forename: John D
authors.initials: JD
authors.lastname: Helmann
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000220:Adaptation, Biological; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D007501:Iron / Q000494:pharmacology*; D050296:Microbial Viability; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009876:Operon / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D007501:Iron; D013385:Succinate Dehydrogenase; D000154:Aconitate Hydratase