title: Genetic and physiological responses of Bacillus subtilis to metal ion stress.
abstract: Metal ion homeostasis is regulated principally by metalloregulatory proteins that control metal ion uptake, storage and efflux genes. We have used transcriptional profiling to survey Bacillus subtilis for genes that are rapidly induced by exposure to high levels of metal ions including Ag(I), Cd(II), Cu(II), Ni(II) and Zn(II) and the metalloid As(V). Many of the genes affected by metal stress were controlled by known metalloregulatory proteins (Fur, MntR, PerR, ArsR and CueR). Additional metal-induced genes are regulated by two newly defined metal-sensing ArsR/SmtB family repressors: CzrA and AseR. CzrA represses the CadA efflux ATPase and the cation diffusion facilitator CzcD and this repression is alleviated by Zn(II), Cd(II), Co(II), Ni(II) and Cu. CadA is the major determinant for Cd(II) resistance, while CzcD protects the cell against elevated levels of Zn(II), Cu, Co(II) and Ni(II). AseR negatively regulates itself and AseA, an As(III) efflux pump which contributes to arsenite resistance in cells lacking a functional ars operon. Our results extend the range of identified effectors for the As(III)-sensor ArsR to include Cd(II) and Ag(I) and for the Cu-sensor CueR to include Ag(I) and, weakly, Cd(II) and Zn(II). In addition to systems dedicated to metal homeostasis, specific metal stresses also strongly induced pathways related to cysteine, histidine and arginine metabolism.
authors.affiliation: Department of Microbiology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Moore
authors.forename: Ahmed
authors.initials: A
authors.lastname: Gaballa
authors.forename: Monica
authors.initials: M
authors.lastname: Hui
authors.forename: Rick W
authors.initials: RW
authors.lastname: Ye
authors.forename: John D
authors.initials: JD
authors.lastname: Helmann
mesh_terms: D000251:Adenosine Triphosphatases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001412:Bacillus subtilis / Q000187:drug effects / Q000502:physiology*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D007477:Ions; D008670:Metals / Q000494:pharmacology*; D009876:Operon; D020917:Receptor, trkA / Q000187:drug effects / Q000235:genetics; D018085:Regulon; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C503087:CzcD protein, Bacillus subtilis; C120278:CzrA protein, Staphylococcus aureus; D004268:DNA-Binding Proteins; D007477:Ions; C051124:MerR protein, Bacteria; D008670:Metals; C433792:MntR protein, bacteria; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C122138:peroxide repressor proteins; D020917:Receptor, trkA; D000251:Adenosine Triphosphatases; C059771:cadmium translocating ATPase