title: Analysis of the Caulobacter crescentus Zur regulon reveals novel insights in zinc acquisition by TonB-dependent outer membrane proteins.
abstract: BACKGROUND
  Intracellular zinc concentration needs to be maintained within strict limits due to its toxicity at high levels, and this is achieved by a finely regulated balance between uptake and efflux. Many bacteria use the Zinc Uptake Regulator Zur to orchestrate zinc homeostasis, but little is known regarding the transport of this metal across the bacterial outer membrane.
  
  
  RESULTS
  In this work we determined the Caulobacter crescentus Zur regulon by global transcriptional and in silico analyses. Among the genes directly repressed by Zur in response to zinc availability are those encoding a putative high affinity ABC uptake system (znuGHI), three TonB-dependent receptors (znuK, znuL and znuM) and one new putative transporter of a family not yet characterized (zrpW). Zur is also directly involved in the activation of a RND and a P-type ATPase efflux systems, as revealed by β-galactosidase and site-directed mutagenesis assays. Several genes belonging to the Fur regulon were also downregulated in the zur mutant, suggesting a putative cross-talk between Zur and Fur regulatory networks. Interestingly, a phenotypic analysis of the znuK and znuL mutants has shown that these genes are essential for growth under zinc starvation, suggesting that C. crescentus uses these TonB-dependent outer membrane transporters as key zinc scavenging systems.
  
  
  CONCLUSIONS
  The characterization of the C. crescentus Zur regulon showed that this regulator coordinates not only uptake, but also the extrusion of zinc. The uptake of zinc by C. crescentus in conditions of scarcity of this metal is highly dependent on TonB-dependent receptors, and the extrusion is mediated by an RND and P-type ATPase transport systems. The absence of Zur causes a disturbance in the dynamic equilibrium of zinc intracellular concentration, which in turn can interfere with other regulatory networks as seen for the Fur regulon.
authors.forename: Ricardo Ruiz
authors.initials: RR
authors.lastname: Mazzon
authors.forename: Vânia Santos
authors.initials: VS
authors.lastname: Braz
authors.forename: José Freire
authors.initials: JF
authors.lastname: da Silva Neto
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av, Prof, Lineu Prestes 1374, 05508-900 São Paulo, Brazil. mvmarque@usp.br.
authors.forename: Marilis
authors.initials: M
authors.lastname: do Valle Marques
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D016935:Caulobacter crescentus / Q000235:genetics / Q000254:growth & development*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015032:Zinc / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; C057616:tonB protein, Bacteria; D015032:Zinc