5. 2011. 25. Aziz RK, Bartels D, Best AA, DeJongh M, Disz T, Edwards RA, Formsma K, Gerdes S,

Glass EM, Kubal M, Meyer F, Olsen GJ, Olson R, Osterman AL, Overbeek RA, McNeil LK, Paarmann D, Paczian T, Parrello B, Pusch GD, Reich C, Stevens Everolimus solubility dmso R, Vassieva O, Vonstein V, Wilke A, Zagnitko O: The RAST Server: Rapid Annotations using Subsystems Technology. BMC Genomics 2008, 9:75.PubMedCrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions RBD and WLS designed the study. RBD performed the analyses and wrote the manuscript. Both RBD and WLS have approved the final manuscript.”
“Background From a physiological point of view, metals fall into three main categories, namely essential and non-toxic (e.g. Ca2+ and Mg2+); essential, but harmful at high concentrations (e.g. Fe2+, Mn2+, Zn2+, Cu2+, Co2+, Ni2+ and Mo2+), and toxic (e.g. Hg2+ or Cd2+) [1]. However, at high concentrations, both essential and find more nonessential metals can be harmful to the cell, damaging the cell membrane, the structure of DNA, or changing the specificity of enzymes [2–4]. The microorganisms have developed homeostasis systems in order to maintain

an optimal intracellular concentration of metals. This is achieved through controlling the processes of transport, intracellular trafficking, efflux and conservation, ensuring its bioavailability to cellular processes and preventing damage to cellular components

[5]. Studies support a role for horizontal gene transfer (HGT) in the evolution of metal homeostasis in Proteobacteria, along with the identification of putative genomic islands (GIs), with examples in Cupriavidus metallidurans, Pseudomonas putida KT2440 and Comamonas testosteroni S44 [6–9]. In fact, many microorganisms have genes located on chromosomes, plasmids, or transposons encoding specific traits conferring resistance to a variety of metal ions [3]. Efflux is one of the main approaches used by bacteria to control internal metal ion concentrations, and several efflux systems have been described in bacteria. The P-type ATPases use ATP hydrolysis to promote ion transport and have been identified in efflux of both mono- and divalent cations from the cytoplasm [10–13]. The Cation Diffusion Facilitator (CDF) are chemiosmotic ion/proton exchangers Cell Cycle inhibitor that present six transmembrane helices and are involved in the efflux of divalent metal cations [11, 14, 15]. In Gram-negative bacteria, the Resistance-Nodulation-Division superfamily (RND) includes systems that confer resistance to antibiotics and metals, and it is composed of a tripartite protein complex: an RND protein, located in the cytoplasmic membrane, a periplasmic membrane fusion protein (MFP) and an outer-membrane channel protein (OMP) [16–18]. These components form a channel that spans both membranes and the periplasmic space [18–21].