All authors read and approved the final manuscript.”
“Background Lead (Pb) is a widely distributed, environmentally persistent, toxic metal. Most bacteria that are tolerant or resistant to lead either precipitate SAR302503 Pb in an insoluble form, or actively export it [1]. Although some metal efflux ATPases, such as ZntA from Escherichia coli, and CadA from Staphylococcus aureus plasmid pI258, can export Pb(II) as well as Zn(II) and Cd(II) [2, 3], the only characterized bacterial Pb(II) specific resistance system is

from Cupriavidus (formerly Wautersia and Ralstonia) metallidurans CH34 [4, 5] – a Gram-negative, multiply metal-resistant, β-proteobacterium originally isolated from a decantation basin at a Belgian zinc production plant (and originally identified as Alcaligenes eutrophus CH34; [6]). Over 150 genes in CH34 are involved in metal resistance, of which at least 70 are carried on the plasmids pMOL28 (171 kb) or pMOL30 (234 kb), and the remainder are carried on the 3.92 Mb chromosome or on a 2.58 Mb second chromosome [7]. Plasmid pMOL30 carries the czc (Cd(II), Zn(II), Co(II)), mer (Hg(II)), STA-9090 in vitro sil (Ag(I)), cop (Cu(II)) and pbr Pb(II) resistance operons [4, 8]. The pbr lead resistance operon from pMOL30 was originally S3I-201 mw predicted to contain

structural genes which encode PbrT, a putative Pb(II) uptake protein belonging to the ILT (Iron Bay 11-7085 Lead Transporter) family [9], a P-type efflux ATPase (PbrA), a predicted inner–membrane protein (PbrB), a predicted prelipoprotein signal peptidase PbrC and a Pb(II) binding protein, PbrD. The regulator of the pbr operon was shown to be PbrR, which is a MerR family regulator [4, 10] Subsequent work has shown that the pbr operon also contains an interrupted orf; pbrU upstream of

pbrT[11, 12] which is predicted to encode a putative inner membrane (Major Facilitator Family MFS1) permease gene, which is probably inactive, but still part of the pbr operon; and that PbrB/PbrC is a fusion protein [11, 12], and encodes an inner membrane bound undecaprenyl pyrophosphate (C55-PP) phosphatase [5]. The pbr operon contains a predicted MerR-like promoter from which pbrRTU are transcribed on one DNA strand, and the pbrABCD genes are transcribed as a polycistronic message on the other [4, 12]. The most recent work on the mechanism of lead resistance encoded by the pMOL30 pbr operon has proposed a model where Pb2+ induces expression of the pMOL30-encoded PbrABCD by PbrR, as well as expression of zinc and cadmium efflux ATPase homologs ZntA and CadA which are carried on the chromosome or second chromosome. Each of these three ATPases is involved in exporting Pb2+ into the periplasm where inorganic phosphates produced by PbrB are involved in precipitating Pb2+ as insoluble lead phosphate.