Abstract
BackgroundIntracellular 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.ResultsIn 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-734) contains supplementary material, which is available to authorized users.
Highlights
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
Construction of a C. crescentus zur mutant strain There are two genes encoding transcriptional regulators belonging to the Fur family annotated in the C. crescentus genome: the well-characterized fur gene, involved in iron homeostasis [26,27] and CC0357, which could encode the zinc uptake regulator Zinc Uptake Regulator (Zur)
Alignment of E. coli, Yersinia pestis, X. campestris and Pseudomonas aeruginosa Zur proteins with the protein encoded by CC0357 shows sequence conservation in Zur-specific residues which are not shared with other members from the Fur family, like Fur and Nur [see Additional file 1: Figure S1]
Summary
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. Zinc, as it occurs with other transition metals, entails a paradox to living cells. A large number of bacteria regulate zinc uptake through Zur (Zinc Uptake Regulator), a regulatory protein belonging to the Fur (Ferric Uptake Regulator) family This metalloprotein contains one structural zinc ion and a second one in its regulatory site per monomer, and acts as a repressor of genes coding for zinc uptake systems under zinc sufficiency [4,5]. Other studies have reported that extrusion systems are regulated in response to zinc in a Zur-dependent manner, as described for Xanthomonas campestris and Corynebacterium glutamicum [8,9,10]
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