We will describe at a molecular level the mechanism of the ubiquitous bacterial plasmid-encoded locus conferring mercury resistance (mer). This very commonly found, but biochemically unusual, detoxification system plays a significant role in the microbial cycling of mercury compounds, including the neurotoxic compound methyl mercury, in nature. The mer operon includes a Hg(II) transport system which delivers the toxic anion to the cytosolic enzyme Hg(II) reductase (HR). HR, which is structurally and mechanistically related to glutathione reductase, reduces Hg(II) to volatile Hg(O) which is comparatively non-toxic. While the HR mechanism is relatively well-understood, the mechanism of the Hg(II) transport system has not been elucidated. The operon is under positive transcriptional control of the merR gene which itself is negatively autoregulated; however, the precise nature of the inducer and the molecular details of operon control are not known. Firstly, genetic and biochemical techniques will be used to examine transcription initiation and termination, mRNA degradation, and the role of translational regulation in operon expression. Secondly, studies of the transport process will be emphasized for their intrinsic interest but also because understanding regulation of operon expression depends on knowing how Hg(II) enters the cell both in the presence and in the absence of mer. Site- or function-specific mutants in all mer genes will be sought by a variety of in vitro and in vivo methods. Finally, several genetic approaches will be used to discover what role the host bacterial cell plays in the expression of mer functions.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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University of Georgia
Schools of Arts and Sciences
United States
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Liebert, C A; Watson, A L; Summers, A O (2000) The quality of merC, a module of the mer mosaic. J Mol Evol 51:607-22
Bass, L; Liebert, C A; Lee, M D et al. (1999) Incidence and characterization of integrons, genetic elements mediating multiple-drug resistance, in avian Escherichia coli. Antimicrob Agents Chemother 43:2925-9
Caguiat, J J; Watson, A L; Summers, A O (1999) Cd(II)-responsive and constitutive mutants implicate a novel domain in MerR. J Bacteriol 181:3462-71
Liebert, C A; Hall, R M; Summers, A O (1999) Transposon Tn21, flagship of the floating genome. Microbiol Mol Biol Rev 63:507-22
Kulkarni, R D; Summers, A O (1999) MerR cross-links to the alpha, beta, and sigma 70 subunits of RNA polymerase in the preinitiation complex at the merTPCAD promoter. Biochemistry 38:3362-8
Bizily, S P; Rugh, C L; Summers, A O et al. (1999) Phytoremediation of methylmercury pollution: merB expression in Arabidopsis thaliana confers resistance to organomercurials. Proc Natl Acad Sci U S A 96:6808-13
Zeng, Q; Stalhandske, C; Anderson, M C et al. (1998) The core metal-recognition domain of MerR. Biochemistry 37:15885-95
Wireman, J; Liebert, C A; Smith, T et al. (1997) Association of mercury resistance with antibiotic resistance in the gram-negative fecal bacteria of primates. Appl Environ Microbiol 63:4494-503
Zeng, Q; Summers, A O (1997) A glutamate uptake regulatory protein (Grp) in Escherichia coli? Mol Microbiol 24:231-2
Zeng, Q; Eidsness, M K; Summers, A O (1997) Near-zero background cloning of PCR products. Biotechniques 23:412-4, 416, 418

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