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YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes.

ABSTRACT: Acquisition and detoxification of metal ions are vital biological processes. Given the requirement of metallochaperones in cellular copper distribution and metallation of cuproproteins, this study investigates whether the metallochaperones also deliver metal ions for transporters functioning in metal detoxification.Resistance to excess cadmium and copper of the yeast Saccharomyces cerevisiae, which is conferred by PCA1 and CaCRP1 metal efflux P-type ATPases, respectively, does not rely on known metallochaperones, Atx1p, Ccs1p, and Cox17p. Copper deficiency induced by the expression of CaCRP1 encoding a copper exporter occurs in the absence of Atx1p. Intriguingly, CCS1 encoding the copper chaperone for superoxide dismutase 1 (Sod1p) is necessary for cadmium resistance that is mediated by Ycf1p, a vacuolar cadmium sequestration transporter. This is attributed to Ccs1p's role in the maturation of Sod1p rather than its direct interaction with Ycf1p for cadmium transfer. Functional defect in Ycf1p associated with the absence of Sod1p as well as another antioxidant enzyme Glr1p is rescued by anaerobic growth or substitutions of specific cysteine residues of Ycf1p to alanine or serine. This further supports oxidative inactivation of Ycf1p in the absence of Ccs1p, Sod1p, or Glr1p.These results provide new insights into the mechanisms of metal metabolism, interaction among metal ions, and the roles for antioxidant systems in metal detoxification.Copper metabolism and antioxidant enzymes maintain the function of Ycf1p for cadmium defense.

SUBMITTER: Wei W

PROVIDER: S-EPMC4158973 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes.

Wei Wenzhong W Smith Nathan N Wu Xiaobin X Kim Heejeong H Seravalli Javier J Khalimonchuk Oleh O Lee Jaekwon J

Antioxidants & redox signaling 20140225 10

<h4>Aims</h4>Acquisition and detoxification of metal ions are vital biological processes. Given the requirement of metallochaperones in cellular copper distribution and metallation of cuproproteins, this study investigates whether the metallochaperones also deliver metal ions for transporters functioning in metal detoxification.<h4>Results</h4>Resistance to excess cadmium and copper of the yeast Saccharomyces cerevisiae, which is conferred by PCA1 and CaCRP1 metal efflux P-type ATPases, respecti ...[more]

PMID: 24444374

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Project description:The greatest challenge of the current generation and generations to come is antimicrobial resistance, as different pathogenic bacteria have continuously evolved to become resistant to even the most recently synthesized antibiotics such as carbapenems. Resistance to carbapenems limits the therapeutic options of MDR infections as they are the only safe and effective drugs recommended to treat such infections. This scenario has complicated treatment outcomes, even to the commonest bacterial infections. Repeated attempts to develop other approaches have been made. The most promising novel therapeutic option is the use of nanomaterials as antimicrobial agents. Thus, this study examined the efficacy of Camellia sinensis extract (CSE) and Prunus africana bark extract (PAE) green synthesized Copper oxide nanoparticles (CuONPs) against carbapenem-resistant bacteria. Furthermore, the photocatalytic and antioxidant activities of CuONPs were evaluated to determine the potential of using them in a wide range of applications. CuONPs were biosynthesized by CSE and PAE. UV vis spectroscopy, X-ray Diffraction (XRD), Dynamic light scattering (DLS), Fourier Transform Infrared spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) were used to characterize the nanoparticles. CuONPs susceptibility tests were carried out by the agar well diffusion method. The photocatalytic and antioxidant activities of the CuONPs were determined by the methylene blue and DPPH free radical scavenging assays, respectively. UV vis absorbance spectra registered surface plasmon resonance peaks between 272 and 286 nm, confirming the presence of CuONPs. The XRD array had nine strong peaks at 2θ values typical of CuONPs. FTIR spectra exhibited bands associated with organic functional groups confirming capping and functionalization of the CuONPs by the phytochemicals. DLS analysis registered a net zeta potential of +12.5 mV. SEM analysis revealed that the nanoparticles were spherical and clustered with a mean diameter of 6 nm. Phytosynthesized CuONPs exhibited the highest growth suppression zones of 30 mm with MIC ranging from 30 to 125 μg/ml against MDR bacteria. Furthermore, the CuONPs achieved a methylene blue dye photocatalysis degradation efficiency of 85.5% and a free radical scavenging activity of 28.8%. PAE and CSE successfully bio-reduced copper ions to the nanoscale level with potent antimicrobial, photocatalysis, and antioxidant activities.

Dataset Information

YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes.

Publications

YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes.

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