Efflux-mediated heavy metal resistance in prokaryotes.

What makes a heavy metal resistant bacterium heavy metal resistant? The mechanisms of action, physiological functions, and distribution of metal-exporting proteins are outlined, namely: CBA efflux pumps driven by proteins of the resistance-nodulation-cell division superfamily, P-type ATPases, cation diffusion facilitator and chromate proteins, NreB- and CnrT-like resistance factors. The complement of efflux systems of 63 sequenced prokaryotes was compared with that of the heavy metal resistant bacterium Ralstonia metallidurans. This comparison shows that heavy metal resistance is the result of multiple layers of resistance systems with overlapping substrate specificities, but unique functions. Some of these systems are widespread and serve in the basic defense of the cell against superfluous heavy metals, but some are highly specialized and occur only in a few bacteria. Possession of the latter systems makes a bacterium heavy metal resistant.

[1]  C. Rensing,et al.  Functional analysis of the Escherichia coli zinc transporter ZitB. , 2002, FEMS microbiology letters.

[2]  S. Walkley,et al.  Metabolic abnormalities in feline Niemann-Pick type C heterozygotes , 1996, Journal of Inherited Metabolic Disease.

[3]  W. Wang,et al.  Two Types of Bacillus subtilis tetA(L) Deletion Strains Reveal the Physiological Importance of TetA(L) in K+ Acquisition as well as in Na+, Alkali, and Tetracycline Resistance , 2000, Journal of bacteriology.

[4]  H. Ohtake,et al.  Cloning, nucleotide sequence, and expression of the chromate resistance determinant of Pseudomonas aeruginosa plasmid pUM505 , 1990, Journal of bacteriology.

[5]  L. Liscum,et al.  Niemann-Pick disease type C. , 1998, Current opinion in lipidology.

[6]  S. Magnet,et al.  Resistance-Nodulation-Cell Division-Type Efflux Pump Involved in Aminoglycoside Resistance in Acinetobacter baumannii Strain BM4454 , 2001, Antimicrobial Agents and Chemotherapy.

[7]  A. Odermatt,et al.  Two trans-Acting Metalloregulatory Proteins Controlling Expression of the Copper-ATPases of Enterococcus hirae* , 1995, The Journal of Biological Chemistry.

[8]  W. Cheung,et al.  Characterization of a Thermophilic P-type Ag+/Cu+-ATPase from the ExtremophileArchaeoglobus fulgidus* , 2002, The Journal of Biological Chemistry.

[9]  J F Harper,et al.  Phylogenetic relationships within cation transporter families of Arabidopsis. , 2001, Plant physiology.

[10]  X. Li,et al.  Organic solvent-tolerant mutants of Pseudomonas aeruginosa display multiple antibiotic resistance. , 1999, Canadian journal of microbiology.

[11]  Dietrich H. Nies,et al.  Regulation of the cnr Cobalt and Nickel Resistance Determinant from Ralstonia sp. Strain CH34 , 2000, Journal of bacteriology.

[12]  M. Saier,et al.  Two novel families of bacterial membrane proteins concerned with nodulation, cell division and transport , 1994, Molecular microbiology.

[13]  Toshihiro Tanaka,et al.  Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5. , 2002, Human molecular genetics.

[14]  C. Rensing,et al.  The zntA gene of Escherichia coli encodes a Zn(II)-translocating P-type ATPase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  P. Hooykaas,et al.  Overexpression of a novel Arabidopsis gene related to putative zinc-transporter genes from animals can lead to enhanced zinc resistance and accumulation. , 1999, Plant physiology.

[16]  S. Clemens,et al.  A Transporter in the Endoplasmic Reticulum ofSchizosaccharomyces pombe Cells Mediates Zinc Storage and Differentially Affects Transition Metal Tolerance* , 2002, The Journal of Biological Chemistry.

[17]  A. Cloeckaert,et al.  Salmonella typhimurium acrB-like gene: identification and role in resistance to biliary salts and detergents and in murine infection. , 1996, FEMS microbiology letters.

[18]  Thomas V. O'Halloran,et al.  The Independent cue and cusSystems Confer Copper Tolerance during Aerobic and Anaerobic Growth inEscherichia coli * , 2001, The Journal of Biological Chemistry.

[19]  H. Mobley,et al.  Helicobacter pylori nickel‐transport gene nixA: synthesis of catalytically active urease in Escherichia coli independent of growth conditions , 1995, Molecular microbiology.

[20]  Kaback Hr Site-Directed Mutagenesis and ION-Gradient Driven Active Transport: On the Path of the Proton , 1988 .

[21]  D. Eide,et al.  Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae , 2000, The EMBO journal.

[22]  D. Nies,et al.  CzcR and CzcD, gene products affecting regulation of resistance to cobalt, zinc, and cadmium (czc system) in Alcaligenes eutrophus , 1992, Journal of bacteriology.

[23]  C. Rensing,et al.  ZitB (YbgR), a Member of the Cation Diffusion Facilitator Family, Is an Additional Zinc Transporter inEscherichia coli , 2001, Journal of bacteriology.

[24]  S. Silver Plasmid-determined metal resistance mechanisms: range and overview. , 1992, Plasmid.

[25]  J. Ecker,et al.  RESPONSIVE-TO-ANTAGONIST1, a Menkes/Wilson Disease–Related Copper Transporter, Is Required for Ethylene Signaling in Arabidopsis , 1999, Cell.

[26]  S. Karlin,et al.  Applications and statistics for multiple high-scoring segments in molecular sequences. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[27]  T. Pembroke,et al.  Isolation of a novel Thermus thermophilus metal efflux protein that improves Escherichia coli growth under stress conditions , 2002, Extremophiles.

[28]  Seon-Woo Lee,et al.  Chromosomal Locus for Cadmium Resistance in Pseudomonas putida Consisting of a Cadmium-Transporting ATPase and a MerR Family Response Regulator , 2001, Applied and Environmental Microbiology.

[29]  M. Saier A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters , 2000, Microbiology and Molecular Biology Reviews.

[30]  D. Nies Heavy metal-resistant bacteria as extremophiles: molecular physiology and biotechnological use of Ralstonia sp. CH34 , 2000, Extremophiles.

[31]  T. Köhler,et al.  Bacterial antibiotic efflux systems of medical importance , 1999, Cellular and Molecular Life Sciences CMLS.

[32]  Dietrich H. Nies,et al.  Alcaligenes eutrophus as a Bacterial Chromate Sensor , 1998, Applied and Environmental Microbiology.

[33]  M. J. LaGier,et al.  Characterization of a heavy metal ATPase from the apicomplexan Cryptosporidium parvum. , 2001, Gene.

[34]  R. Stowe,et al.  Psychosis as a presentation of physical disease in adolescence: a case of Niemann–Pick disease, type C , 1998, Developmental medicine and child neurology.

[35]  M. Mergeay,et al.  Ralstonia metallidurans, a bacterium specifically adapted to toxic metals: towards a catalogue of metal-responsive genes. , 2003, FEMS microbiology reviews.

[36]  M. Tsuda,et al.  Characterization of the MexC-MexD-OprJ Multidrug Efflux System in ΔmexA-mexB-oprM Mutants of Pseudomonas aeruginosa , 1998, Antimicrobial Agents and Chemotherapy.

[37]  M. Varela,et al.  Molecular biology of the lactose carrier of Escherichia coli. , 1996, Biochimica et biophysica acta.

[38]  J. Martínez,et al.  Stenotrophomonas maltophilia D457R Contains a Cluster of Genes from Gram-Positive Bacteria Involved in Antibiotic and Heavy Metal Resistance , 2000, Antimicrobial Agents and Chemotherapy.

[39]  R. Palmiter,et al.  ZnT‐2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration. , 1996, The EMBO journal.

[40]  M H Saier,et al.  A family of gram-negative bacterial outer membrane factors that function in the export of proteins, carbohydrates, drugs and heavy metals from gram-negative bacteria. , 1997, FEMS microbiology letters.

[41]  N. Vats,et al.  Characterization of a copper-transport operon, copYAZ, from Streptococcus mutans. , 2001, Microbiology.

[42]  W. B. Adams,et al.  Occurrence of glutathione in bacteria , 1978, Journal of bacteriology.

[43]  S. Bröer,et al.  Arsenic efflux governed by the arsenic resistance determinant of Staphylococcus aureus plasmid pI258 , 1993, Journal of bacteriology.

[44]  W. Ernst,et al.  Metal tolerance in plants , 1992 .

[45]  N. Brown,et al.  Two-Component Systems in the Regulation of Heavy Metal Resistance , 1998 .

[46]  C. Elkins,et al.  Substrate Specificity of the RND-Type Multidrug Efflux Pumps AcrB and AcrD of Escherichia coli Is Determined Predominately by Two Large Periplasmic Loops , 2002, Journal of bacteriology.

[47]  Lori A. S. Snyder,et al.  The MtrD protein of Neisseria gonorrhoeae is a member of the resistance/nodulation/division protein family constituting part of an efflux system. , 1997, Microbiology.

[48]  H. Maseda,et al.  The outer membrane component of the multidrug efflux pump from Pseudomonas aeruginosa may be a gated channel. , 2002, European journal of biochemistry.

[49]  K. Entian,et al.  Investigation of the yvgW Bacillus subtilis chromosomal gene involved in Cd(2+) ion resistance. , 2002, FEMS microbiology letters.

[50]  N. Brown,et al.  Transcriptional Organization of the czcHeavy-Metal Homeostasis Determinant from Alcaligenes eutrophus , 1999, Journal of bacteriology.

[51]  G. Grass,et al.  The product of the ybdE gene of the Escherichia coli chromosome is involved in detoxification of silver ions. , 2001, Microbiology.

[52]  M. Solioz,et al.  The Enterococcus hirae paradigm of copper homeostasis: Copper chaperone turnover, interactions, and transactions , 2003, Biometals.

[53]  D. Eide,et al.  Biochemical Properties of Vacuolar Zinc Transport Systems ofSaccharomyces cerevisiae * , 2002, The Journal of Biological Chemistry.

[54]  M. Dobson,et al.  The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1. , 1998, American journal of human genetics.

[55]  K. Poole,et al.  Role of the Multidrug Efflux Systems ofPseudomonas aeruginosa in Organic Solvent Tolerance , 1998, Journal of bacteriology.

[56]  M. Ehrmann,et al.  Membrane Topology of the Xenobiotic-exporting Subunit, MexB, of the MexA,B-OprM Extrusion Pump in Pseudomonas aeruginosa * , 1999, The Journal of Biological Chemistry.

[57]  H. Liesegang,et al.  Characterization of the inducible nickel and cobalt resistance determinant cnr from pMOL28 of Alcaligenes eutrophus CH34 , 1993, Journal of bacteriology.

[58]  J. Mathers,et al.  A Novel Zinc-regulated Human Zinc Transporter, hZTL1, Is Localized to the Enterocyte Apical Membrane* , 2002, The Journal of Biological Chemistry.

[59]  N. Brown,et al.  Copper-resistant enteric bacteria from United Kingdom and Australian piggeries , 1993, Applied and environmental microbiology.

[60]  S. Steinberg,et al.  Co-cultivation of Niemann-Pick disease type C fibroblasts belonging to complementation groupsα andβ stimulates LDL-derived cholesterol esterification , 1996, Journal of Inherited Metabolic Disease.

[61]  C. Outten,et al.  Femtomolar Sensitivity of Metalloregulatory Proteins Controlling Zinc Homeostasis , 2001, Science.

[62]  S. Izawa,et al.  Expression of ZRC1 coding for suppressor of zinc toxicity is induced by zinc-starvation stress in Zap1-dependent fashion in Saccharomyces cerevisiae. , 2000, Biochemical and biophysical research communications.

[63]  M Mergeay,et al.  Two‐component regulatory system involved in transcriptional control of heavy‐metal homoeostasis in Alcaligenes eutrophus , 1997, Molecular microbiology.

[64]  H. Sasaki,et al.  Deficiencies of hippocampal Zn and ZnT3 accelerate brain aging of Rat. , 2000, Biochemical and biophysical research communications.

[65]  P A Midgley,et al.  Magnetite morphology and life on Mars , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[66]  S. Silver,et al.  CadC, the transcriptional regulatory protein of the cadmium resistance system of Staphylococcus aureus plasmid pI258 , 1995, Journal of bacteriology.

[67]  N. Robinson,et al.  Zn, Cu and Co in cyanobacteria: selective control of metal availability. , 2003, FEMS microbiology reviews.

[68]  M H Saier,et al.  Unified inventory of established and putative transporters encoded within the complete genome of Saccharomyces cerevisiae , 1998, FEBS letters.

[69]  N. Brown,et al.  Bacterial resistances to mercury and copper , 1991, Journal of cellular biochemistry.

[70]  L. Que,et al.  Zinc Binding to the NH2-terminal Domain of the Wilson Disease Copper-transporting ATPase , 2002, The Journal of Biological Chemistry.

[71]  D. Salt,et al.  Functional activity and role of cation-efflux family members in Ni hyperaccumulation in Thlaspi goesingense , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[72]  N. Brown,et al.  The nucleotide sequence of the mercuric resistance operons of plasmid R100 and transposon Tn501: further evidence for mer genes which enhance the activity of the mercuric ion detoxification system , 2004, Molecular and General Genetics MGG.

[73]  D. Nies,et al.  Microbial heavy-metal resistance , 1999, Applied Microbiology and Biotechnology.

[74]  O. Lenz,et al.  The Alcaligenes eutrophus H16 hoxX gene participates in hydrogenase regulation , 1994, Journal of bacteriology.

[75]  P. Ueland,et al.  Hyperhomocysteinemia in terms of steady-state kinetics , 1998, European Journal of Pediatrics.

[76]  T. Logan,et al.  Involvement of gamma-glutamyl peptides in osmoadaptation of Escherichia coli , 1990, Journal of bacteriology.

[77]  Ana Segura,et al.  Mechanisms of solvent tolerance in gram-negative bacteria. , 2002, Annual review of microbiology.

[78]  K. Poole,et al.  β-Lactamase Inhibitors Are Substrates for the Multidrug Efflux Pumps of Pseudomonas aeruginosa , 1998, Antimicrobial Agents and Chemotherapy.

[79]  Kazuaki Matsui,et al.  Molecular basis for resistance to silver cations in Salmonella , 1999, Nature Medicine.

[80]  R. Palmiter,et al.  ZnT-3, a putative transporter of zinc into synaptic vesicles. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[81]  I. Paulsen,et al.  A Novel Family of Ubiquitous Heavy Metal Ion Transport Proteins , 1997, The Journal of Membrane Biology.

[82]  B. Iglewski,et al.  Active Efflux and Diffusion Are Involved in Transport of Pseudomonas aeruginosa Cell-to-Cell Signals , 1999, Journal of bacteriology.

[83]  G. Węgrzyn,et al.  Inactivation of the acrA gene is partially responsible for chloramphenicol sensitivity of Escherichia coli CM2555 strain expressing the chloramphenicol acetyltransferase gene. , 2002, Microbial drug resistance.

[84]  K. Poole,et al.  Expression of Pseudomonas aeruginosa Multidrug Efflux Pumps MexA-MexB-OprM and MexC-MexD-OprJ in a Multidrug-Sensitive Escherichia coli Strain , 1998, Antimicrobial Agents and Chemotherapy.

[85]  W. Shafer,et al.  Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae , 2002, Journal of bacteriology.

[86]  F. Guillain,et al.  A possible regulatory role for the metal‐binding domain of CadA, the Listeria monocytogenes Cd2+‐ATPase , 2001, FEBS letters.

[87]  R. Erickson,et al.  Increased expression of caveolin-1 in heterozygous Niemann-Pick type II human fibroblasts. , 1997, Biochemical and biophysical research communications.

[88]  J. Helmann,et al.  A peroxide‐induced zinc uptake system plays an important role in protection against oxidative stress in Bacillus subtilis , 2002, Molecular microbiology.

[89]  H. Mobley,et al.  Helicobacter pylori cadA encodes an essential Cd(II)–Zn(II)–Co(II) resistance factor influencing urease activity , 1999, Molecular microbiology.

[90]  S. Nakashima,et al.  A Novel Histidine-Rich CPx-ATPase from the Filamentous Cyanobacterium Oscillatoria brevis Related to Multiple-Heavy-Metal Cotolerance , 2002, Journal of bacteriology.

[91]  Hiroshi Nikaido,et al.  Multidrug resistance mechanisms: drug efflux across two membranes , 2000, Molecular microbiology.

[92]  K. Poole,et al.  The outer membrane protein OprM of Pseudomonas aeruginosa is encoded by oprK of the mexA-mexB-oprK multidrug resistance operon , 1995, Antimicrobial agents and chemotherapy.

[93]  E. Kothe,et al.  Evidence for high affinity nickel transporter genes in heavy metal resistant Streptomyces spec. , 2000, Journal of basic microbiology.

[94]  R. Schiffmann Niemann-Pick disease type C. From bench to bedside. , 1996, JAMA.

[95]  M. D. Snavely,et al.  Magnesium transport in Salmonella typhimurium: 28Mg2+ transport by the CorA, MgtA, and MgtB systems , 1989, Journal of bacteriology.

[96]  I. Bertini,et al.  Solution structure of the N-terminal domain of a potential copper-translocating P-type ATPase from Bacillus subtilis in the apo and Cu(I) loaded states. , 2002, Journal of molecular biology.

[97]  H. Zgurskaya,et al.  Chimeric Analysis of the Multicomponent Multidrug Efflux Transporters from Gram-Negative Bacteria , 2002, Journal of bacteriology.

[98]  R. Erickson,et al.  Altered expression of caveolin-1 and increased cholesterol in detergent insoluble membrane fractions from liver in mice with Niemann-Pick disease type C. , 1997, Biochimica et biophysica acta.

[99]  B. Shuckett,et al.  Pulmonary infiltration in Niemann-Pick disease type C , 1996, Journal of Inherited Metabolic Disease.

[100]  K. Bissig,et al.  Tetrathiomolybdate inhibition of the Enterococcus hirae CopB copper ATPase , 2001, FEBS letters.

[101]  S. J. Beard,et al.  Zinc(II) tolerance in Escherichia coli K‐12: evidence that the zntA gene (o732) encodes a cation transport ATPase , 1997, Molecular microbiology.

[102]  C. van Delden,et al.  Amino Acid Residues Essential for Function of the MexF Efflux Pump Protein of Pseudomonas aeruginosa , 2002, Antimicrobial Agents and Chemotherapy.

[103]  M. Saier,et al.  Computer-aided analyses of transport protein sequences: gleaning evidence concerning function, structure, biogenesis, and evolution , 1994, Microbiological reviews.

[104]  Liping Huang,et al.  Functional Characterization of a Novel Mammalian Zinc Transporter, ZnT6* , 2002, The Journal of Biological Chemistry.

[105]  N. C. Price,et al.  Purification and characterization of the periplasmic nickel-binding protein NikA of Escherichia coli K12. , 1995, European journal of biochemistry.

[106]  S. Silver,et al.  Nucleotide sequence and expression of a plasmid-encoded chromate resistance determinant from Alcaligenes eutrophus. , 1990, The Journal of biological chemistry.

[107]  M Mergeay,et al.  Classification of metal-resistant bacteria from industrial biotopes as Ralstonia campinensis sp. nov., Ralstonia metallidurans sp. nov. and Ralstonia basilensis Steinle et al. 1998 emend. , 2001, International journal of systematic and evolutionary microbiology.

[108]  X. Li,et al.  Inner membrane efflux components are responsible for beta-lactam specificity of multidrug efflux pumps in Pseudomonas aeruginosa , 1997, Journal of bacteriology.

[109]  N. Brown,et al.  The Pco proteins are involved in periplasmic copper handling in Escherichia coli. , 2002, Biochemical and biophysical research communications.

[110]  G. Dallner,et al.  Peroxisomal Impairment in Niemann-Pick Type C Disease* , 1997, The Journal of Biological Chemistry.

[111]  H. Nikaido,et al.  AcrA is a highly asymmetric protein capable of spanning the periplasm. , 1999, Journal of molecular biology.

[112]  A. Viarengo,et al.  Occurrence of Cu-ATPase in Dictyostelium: possible role in resistance to copper. , 2002, Biochemical and biophysical research communications.

[113]  T. Iwanaga,et al.  Cloning and Characterization of a Novel Mammalian Zinc Transporter, Zinc Transporter 5, Abundantly Expressed in Pancreatic β Cells* , 2002, The Journal of Biological Chemistry.

[114]  C. Rensing,et al.  Pb(II)-translocating P-type ATPases* , 1998, The Journal of Biological Chemistry.

[115]  R. Jayaswal,et al.  Molecular Characterization of a Chromosomal Determinant Conferring Resistance to Zinc and Cobalt Ions inStaphylococcus aureus , 1998, Journal of bacteriology.

[116]  S. Silver,et al.  Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. , 2003, FEMS microbiology reviews.

[117]  G. Church,et al.  Alignment and structure prediction of divergent protein families: periplasmic and outer membrane proteins of bacterial efflux pumps. , 1999, Journal of molecular biology.

[118]  A. Alonso,et al.  Cloning and Characterization of SmeDEF, a Novel Multidrug Efflux Pump from Stenotrophomonas maltophilia , 2000, Antimicrobial Agents and Chemotherapy.

[119]  T. Murata,et al.  The substrate specificity of tripartite efflux systems of Pseudomonas aeruginosa is determined by the RND component. , 2002, Biochemical and biophysical research communications.

[120]  H. Kaback,et al.  Helix packing in polytopic membrane proteins: the lactose permease of Escherichia coli. , 1997, Current opinion in structural biology.

[121]  S. Silver,et al.  Bacterial Plasmid-Mediated Resistances to Mercury, Cadmium, and Copper , 1995 .

[122]  D. Nies,et al.  The cobalt, zinc, and cadmium efflux system CzcABC from Alcaligenes eutrophus functions as a cation-proton antiporter in Escherichia coli , 1995, Journal of bacteriology.

[123]  A. Vellodi,et al.  Niemann–Pick disease type C and defective peroxisomal β-oxidation of branched-chain substrates , 1998, Journal of Inherited Metabolic Disease.

[124]  H. Nikaido,et al.  Multiple antibiotic resistance and efflux. , 1998, Current opinion in microbiology.

[125]  M. Mergeay,et al.  Regulation of the cnr Cobalt and Nickel Resistance Determinant of Ralstonia eutropha (Alcaligenes eutrophus) CH34 , 2000, Journal of bacteriology.

[126]  O. Degen,et al.  Substrate Specificity of Nickel/Cobalt Permeases: Insights from Mutants Altered in Transmembrane Domains I and II , 2002, Journal of bacteriology.

[127]  A. Yamaguchi,et al.  Analysis of a Complete Library of Putative Drug Transporter Genes in Escherichia coli , 2001, Journal of bacteriology.

[128]  C. Rensing,et al.  CopA: An Escherichia coli Cu(I)-translocating P-type ATPase. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[129]  H. Nikaido,et al.  Bypassing the periplasm: reconstitution of the AcrAB multidrug efflux pump of Escherichia coli. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[130]  Qijing Zhang,et al.  CmeABC Functions as a Multidrug Efflux System in Campylobacter jejuni , 2002, Antimicrobial Agents and Chemotherapy.

[131]  D. Persson,et al.  Copper(I) complexes of penicillamine and glutathione. , 1979, Journal of inorganic biochemistry.

[132]  J. Piškur Transmission of the yeast mitochondrial genome to progeny: The impact of intergenic sequences , 1989, Molecular and General Genetics MGG.

[133]  H. Yoneyama,et al.  Subunit swapping in the Mex-extrusion pumps in Pseudomonas aeruginosa. , 1998, Biochemical and biophysical research communications.

[134]  H. Ohtake,et al.  Decreased chromate uptake in Pseudomonas fluorescens carrying a chromate resistance plasmid , 1987, Journal of bacteriology.

[135]  H. Fu,et al.  Membrane Topology of the pl258 CadA Cd(II)/Pb(II)/Zn(II)-Translocating P-Type ATPase , 2002, Journal of bioenergetics and biomembranes.

[136]  T. Köhler,et al.  In Vivo Emergence of Multidrug-Resistant Mutants ofPseudomonas aeruginosa Overexpressing the Active Efflux System MexA-MexB-OprM , 1999, Antimicrobial Agents and Chemotherapy.

[137]  C. Kumamoto,et al.  Role of a Candida albicans P1-Type ATPase in Resistance to Copper and Silver Ion Toxicity , 2000, Journal of bacteriology.

[138]  J. Hearst,et al.  Molecular cloning and characterization of acrA and acrE genes of Escherichia coli , 1993, Journal of bacteriology.

[139]  K. G. Coleman,et al.  Substantial narrowing of the Niemann-Pick C candidate interval by yeast artificial chromosome complementation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[140]  K. Bissig,et al.  Structure-function analysis of purified Enterococcus hirae CopB copper ATPase: effect of Menkes/Wilson disease mutation homologues. , 2001 .

[141]  R. Palmiter,et al.  Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. , 1995, The EMBO journal.

[142]  S. Swarup,et al.  Molecular characterization of an operon, cueAR, encoding a putative P1-type ATPase and a MerR-type regulatory protein involved in copper homeostasis in Pseudomonas putida. , 2002, Microbiology.

[143]  A. Odermatt,et al.  An ATPase Operon Involved in Copper Resistance by Enterococcus hirae a , 1992, Annals of the New York Academy of Sciences.

[144]  S. Clemens,et al.  Characterization of the ZAT1p zinc transporter from Arabidopsis thaliana in microbial model organisms and reconstituted proteoliposomes , 2002, Planta.

[145]  S. Izawa,et al.  The Zrc1 is involved in zinc transport system between vacuole and cytosol in Saccharomyces cerevisiae. , 2001, Biochemical and biophysical research communications.

[146]  T. O’Halloran,et al.  Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. , 1999, Science.

[147]  D. Huffman,et al.  Spectroscopy of Cu(II)-PcoC and the multicopper oxidase function of PcoA, two essential components of Escherichia coli pco copper resistance operon. , 2002, Biochemistry.

[148]  C. Anthon,et al.  A Ni2+ Binding Motif Is the Basis of High Affinity Transport of the Alcaligenes eutrophus Nickel Permease* , 1997, The Journal of Biological Chemistry.

[149]  S. Silver,et al.  Cloning and expression of plasmid genes encoding resistances to chromate and cobalt in Alcaligenes eutrophus , 1989, Journal of bacteriology.

[150]  L. Guilloteau,et al.  Functional Characterization of Brucella melitensis NorMI, an Efflux Pump Belonging to the Multidrug and Toxic Compound Extrusion Family , 2002, Antimicrobial Agents and Chemotherapy.

[151]  C. Rensing,et al.  Escherichia coli mechanisms of copper homeostasis in a changing environment. , 2003, FEMS microbiology reviews.

[152]  Colin Hughes,et al.  Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export , 2000, Nature.

[153]  R. Moreno-Sánchez,et al.  Efflux of chromate by Pseudomonas aeruginosa cells expressing the ChrA protein. , 2002, FEMS microbiology letters.

[154]  G. Nucifora,et al.  Cadmium resistance from Staphylococcus aureus plasmid pI258 cadA gene results from a cadmium-efflux ATPase. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[155]  W. Peng,et al.  Characterization of a putative RND-type efflux system in Agrobacterium tumefaciens. , 2001, Gene.

[156]  M. Inouhe,et al.  The cadmium-resistant gene, CAD2, which is a mutated putative copper-transporter gene (PCA1), controls the intracellular cadmium-level in the yeast S. cerevisiae , 2000, Current Genetics.

[157]  H. Nikaido,et al.  The acrAB homolog of Haemophilus influenzae codes for a functional multidrug efflux pump , 1997, Journal of bacteriology.

[158]  N. Brown,et al.  Copper resistance determinants in bacteria. , 1992, Plasmid.

[159]  C. Rensing,et al.  The ATP Hydrolytic Activity of Purified ZntA, a Pb(II)/Cd(II)/Zn(II)-translocating ATPase from Escherichia coli * , 2000, The Journal of Biological Chemistry.

[160]  S. Silver Bacterial plasmid resistances to copper, cadmium, and zinc , 1993 .

[161]  N. McIntyre,et al.  Molecular diagnosis of Wilson disease. , 2001, Molecular genetics and metabolism.

[162]  K. Poole,et al.  The MexA-MexB-OprM multidrug efflux system of Pseudomonas aeruginosa is growth-phase regulated. , 1999, FEMS microbiology letters.

[163]  Ludo Diels,et al.  DNA Probe-Mediated Detection of Resistant Bacteria from Soils Highly Polluted by Heavy Metals , 1990, Applied and environmental microbiology.

[164]  Ramesh C. Patel,et al.  Cellular Cholesterol Storage in the Niemann‐Pick Disease Type C Mouse Is Associated with Increased Expression and Defective Processing of Apolipoprotein D , 1998, Journal of neurochemistry.

[165]  A. J. Ablooglu,et al.  A Bacillus subtilis locus encoding several gene products affecting transport of cations. , 1997, Gene.

[166]  M. Mergeay,et al.  Cloning of plasmid genes encoding resistance to cadmium, zinc, and cobalt in Alcaligenes eutrophus CH34 , 1987, Journal of bacteriology.

[167]  M. Zagorec,et al.  Development of Genetic Tools forLactobacillus sakei: Disruption of the β-Galactosidase Gene and Use of lacZ as a Reporter Gene To Study Regulation of the Putative Copper ATPase, AtkB , 2000, Applied and Environmental Microbiology.

[168]  R. England,et al.  Increased expression of the multidrug efflux genes acrAB occurs during slow growth of Escherichia coli. , 2002, FEMS microbiology letters.

[169]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[170]  D. Nies,et al.  Energetics and Topology of CzcA, a Cation/Proton Antiporter of the Resistance-Nodulation-Cell Division Protein Family* , 1999, Journal of Biological Chemistry.

[171]  L. Dominey,et al.  Kinetics and mechanism of Zn(II) complexation with reduced glutathione. , 1983, Journal of inorganic biochemistry.

[172]  K. Axelsen,et al.  Inventory of the superfamily of P-type ion pumps in Arabidopsis. , 2001, Plant physiology.

[173]  Angela Lee,et al.  Use of a Genetic Approach To Evaluate the Consequences of Inhibition of Efflux Pumps in Pseudomonas aeruginosa , 1999, Antimicrobial Agents and Chemotherapy.

[174]  M. Saier,et al.  P-type ATPases of eukaryotes and bacteria: Sequence analyses and construction of phylogenetic trees , 2004, Journal of Molecular Evolution.

[175]  B. Friedrich,et al.  A topological model for the high‐affinity nickel transporter of Alcaligenes eutrophus , 1994, Molecular microbiology.

[176]  M. Saier,et al.  CHR, a Novel Family of Prokaryotic Proton Motive Force-Driven Transporters Probably Containing Chromate/Sulfate Antiporters , 1998, Journal of bacteriology.

[177]  Thomas V. O'Halloran,et al.  Identification of a Copper-Responsive Two-Component System on the Chromosome of Escherichia coli K-12 , 2000, Journal of bacteriology.

[178]  Role of multiple efflux pumps in Escherichia coli in indole expulsion. , 1999, FEMS microbiology letters.

[179]  K. Senoo,et al.  Cloning and sequence analysis of czc genes in Alcaligenes sp. strain CT14. , 1996, Bioscience, biotechnology, and biochemistry.

[180]  A. Odermatt,et al.  Induction of the putative copper ATPases, CopA and CopB, of Enterococcus hirae by Ag+ and Cu2+, and Ag+ extrusion by CopB. , 1994, Biochemical and biophysical research communications.

[181]  H. Schweizer,et al.  The MexJK Efflux Pump of Pseudomonas aeruginosa Requires OprM for Antibiotic Efflux but Not for Efflux of Triclosan , 2002, Journal of bacteriology.

[182]  R. Moreno-Sánchez,et al.  Chromate Efflux by Means of the ChrA Chromate Resistance Protein from Pseudomonas aeruginosa , 1999, Journal of bacteriology.

[183]  M. Solioz,et al.  Copper homeostasis in Enterococcus hirae. , 2003, FEMS microbiology reviews.

[184]  R. Palmiter,et al.  Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[185]  A. Odermatt,et al.  Primary structure of two P-type ATPases involved in copper homeostasis in Enterococcus hirae. , 1993, The Journal of biological chemistry.

[186]  D. Nies,et al.  CzcD Is a Heavy Metal Ion Transporter Involved in Regulation of Heavy Metal Resistance in Ralstonia sp. Strain CH34 , 1999, Journal of bacteriology.

[187]  J. Lanyi,et al.  A linkage of the pKa's of asp-85 and glu-204 forms part of the reprotonation switch of bacteriorhodopsin. , 1996, Biochemistry.

[188]  S. Silver,et al.  Newer systems for bacterial resistances to toxic heavy metals. , 1994, Environmental health perspectives.

[189]  G. Girouard,et al.  Linkage of Niemann-Pick disease type D to the same region of human chromosome 18 as Niemann-Pick disease type C. , 1997, American journal of human genetics.

[190]  C. Andersen,et al.  An aspartate ring at the TolC tunnel entrance determines ion selectivity and presents a target for blocking by large cations , 2002, Molecular microbiology.

[191]  M. Vanier,et al.  Early-lethal pulmonary form of Niemann-Pick type C disease belonging to a second, rare genetic complementation group , 1998, European Journal of Pediatrics.

[192]  Liangtao Li,et al.  The Yeast Gene MSC2, a Member of the Cation Diffusion Facilitator Family, Affects the Cellular Distribution of Zinc* , 2001, The Journal of Biological Chemistry.

[193]  Q. Fernaǹdo,et al.  The formation of constants of mercury(II)--glutathione complexes. , 1996, Chemical research in toxicology.

[194]  Joseph L. Kirschvink,et al.  Magnetofossils from Ancient Mars: a Robust Biosignature in the Martian Meteorite ALH84001 , 2002, Applied and Environmental Microbiology.

[195]  C. Andersen,et al.  Protein export and drug efflux through bacterial channel-tunnels. , 2001, Current opinion in cell biology.

[196]  J. Rutherford,et al.  Cobalt-dependent Transcriptional Switching by a Dual-effector MerR-like Protein Regulates a Cobalt-exporting Variant CPx-type ATPase* , 1999, The Journal of Biological Chemistry.

[197]  E. Nogales,et al.  Lipid-layer crystallization and preliminary three-dimensional structural analysis of AcrA, the periplasmic component of a bacterial multidrug efflux pump. , 2001, Journal of structural biology.

[198]  S. Silver,et al.  Microbial arsenic: from geocycles to genes and enzymes. , 2002, FEMS microbiology reviews.

[199]  Mark G. M. Aarts,et al.  Elevated expression of metal transporter genes in three accessions of the metal hyperaccumulator Thlaspi caerulescens , 2001 .

[200]  C. Rensing,et al.  Genes Involved in Copper Homeostasis inEscherichia coli , 2001, Journal of bacteriology.

[201]  H. Nikaido,et al.  AcrD of Escherichia coli Is an Aminoglycoside Efflux Pump , 2000, Journal of bacteriology.

[202]  B. Mossman,et al.  Oxygen radicals and asbestos-mediated disease. , 1994, Environmental health perspectives.

[203]  S. Silver,et al.  Expression and nucleotide sequence of a plasmid-determined divalent cation efflux system from Alcaligenes eutrophus. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[204]  N. Brown,et al.  Molecular genetics and transport analysis of the copper‐resistance determinant (pco) from Escherichia coli plasmid pRJ1004 , 1995, Molecular microbiology.

[205]  H. Nikaido,et al.  Cross-Linked Complex between Oligomeric Periplasmic Lipoprotein AcrA and the Inner-Membrane-Associated Multidrug Efflux Pump AcrB from Escherichia coli , 2000, Journal of bacteriology.

[206]  R. Gardner,et al.  Overexpression of the Saccharomyces cerevisiaeMagnesium Transport System Confers Resistance to Aluminum Ion* , 1998, The Journal of Biological Chemistry.

[207]  C. Kung,et al.  COT1, a gene involved in cobalt accumulation in Saccharomyces cerevisiae , 1992, Molecular and cellular biology.

[208]  S. Levy,et al.  Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli , 1997, Journal of bacteriology.

[209]  Ayush Kumar,et al.  Fluoroquinolone resistance of Serratia marcescens: involvement of a proton gradient-dependent efflux pump. , 2002, The Journal of antimicrobial chemotherapy.

[210]  Luis López-Maury,et al.  A two‐component signal transduction system involved in nickel sensing in the cyanobacterium Synechocystis sp. PCC 6803 , 2002, Molecular microbiology.

[211]  P. Plésiat,et al.  Mechanisms of beta-lactam resistance in Pseudomonas aeruginosa: prevalence of OprM-overproducing strains in a French multicentre study (1997). , 2002, The Journal of antimicrobial chemotherapy.

[212]  C. Rensing,et al.  NreB from Achromobacter xylosoxidans 31A Is a Nickel-Induced Transporter Conferring Nickel Resistance , 2001, Journal of bacteriology.

[213]  H. Nikaido,et al.  Active efflux of bile salts by Escherichia coli , 1997, Journal of bacteriology.

[214]  D. Nies,et al.  New genes involved in chromate resistance inRalstonia metallidurans strain CH34 , 2002, Archives of Microbiology.

[215]  H. Schlegel,et al.  Plasmid pMOL28-encoded resistance to nickel is due to specific efflux , 1988 .

[216]  P. Cornelis,et al.  Characterization of a new efflux pump, MexGHI-OpmD, from Pseudomonas aeruginosa that confers resistance to vanadium. , 2002, Microbiology.

[217]  D. Nies,et al.  First step towards a quantitative model describing Czc-mediated heavy metal resistance in Ralstonia metallidurans , 2003, Biodegradation.

[218]  A Yamaguchi,et al.  Molecular construction of a multidrug exporter system, AcrAB: molecular interaction between AcrA and AcrB, and cleavage of the N-terminal signal sequence of AcrA. , 2000, Journal of biochemistry.

[219]  T. Steck,et al.  Four cholesterol-sensing proteins. , 1998, Current opinion in structural biology.

[220]  Christina Cramer,et al.  Antibiotic Susceptibility Profiles ofEscherichia coli Strains Lacking Multidrug Efflux Pump Genes , 2001, Antimicrobial Agents and Chemotherapy.

[221]  S. Silver,et al.  Plasmid-determined inducible efflux is responsible for resistance to cadmium, zinc, and cobalt in Alcaligenes eutrophus , 1989, Journal of bacteriology.

[222]  P. Rich,et al.  Two Menkes-type ATPases Supply Copper for Photosynthesis inSynechocystis PCC 6803* , 2001, The Journal of Biological Chemistry.

[223]  Liangtao Li,et al.  Characterization of Two Homologous Yeast Genes That Encode Mitochondrial Iron Transporters* , 1997, The Journal of Biological Chemistry.

[224]  N. Brown,et al.  Bacterial transport of and resistance to copper , 1994 .

[225]  H. Mobley,et al.  Conserved Residues and Motifs in the NixA Protein ofHelicobacter pylori Are Critical for the High Affinity Transport of Nickel Ions* , 1998, The Journal of Biological Chemistry.

[226]  N. Brown,et al.  Copper-inducible transcriptional regulation at two promoters in the Escherichia coli copper resistance determinant pco. , 1997, Microbiology.

[227]  B. Mitra,et al.  The cysteine-rich amino-terminal domain of ZntA, a Pb(II)/Zn(II)/Cd(II)-translocating ATPase from Escherichia coli, is not essential for its function. , 2001, Biochemistry.

[228]  Purification, crystallization and preliminary diffraction studies of AcrB, an inner-membrane multi-drug efflux protein. , 2002, Acta crystallographica. Section D, Biological crystallography.

[229]  F. Aarestrup,et al.  tcrB, a Gene Conferring Transferable Copper Resistance in Enterococcus faecium: Occurrence, Transferability, and Linkage to Macrolide and Glycopeptide Resistance , 2002, Antimicrobial Agents and Chemotherapy.

[230]  J. Rosenfeld,et al.  Related membrane domains in proteins of sterol sensing and cell signaling provide a glimpse of treasures still buried within the dynamic realm of intracellular metabolic regulation. , 1998, Current opinion in lipidology.

[231]  S. Silver,et al.  Bacterial heavy metal resistance: new surprises. , 1996, Annual review of microbiology.

[232]  C. Kung,et al.  Interactions between gene products involved in divalent cation transport in Saccharomyces cerevisiae , 1994, Molecular and General Genetics MGG.

[233]  H. Yoneyama,et al.  Assignment of the Substrate-Selective Subunits of the MexEF-OprN Multidrug Efflux Pump of Pseudomonas aeruginosa , 2000, Antimicrobial Agents and Chemotherapy.

[234]  T. A. Krulwich,et al.  An antiport mechanism for a member of the cation diffusion facilitator family: divalent cations efflux in exchange for K+ and H+ , 2002, Molecular microbiology.

[235]  N. Brown,et al.  Cloning and Functional Analysis of thepbr Lead Resistance Determinant of Ralstonia metallidurans CH34 , 2001, Journal of bacteriology.

[236]  Satoshi Murakami,et al.  Crystal structure of bacterial multidrug efflux transporter AcrB , 2002, Nature.

[237]  R. C. Fahey,et al.  Novel thiols of prokaryotes. , 2001, Annual review of microbiology.

[238]  N. Brown,et al.  Bacterial Response to Copper in the Environment: Copper Resistance in Escherichia coli as a Model System , 1990 .

[239]  Hiroshi Nikaido,et al.  Multidrug Efflux Pump AcrAB of Salmonella typhimuriumExcretes Only Those β-Lactam Antibiotics Containing Lipophilic Side Chains , 1998, Journal of bacteriology.

[240]  C. Rensing,et al.  New functions for the three subunits of the CzcCBA cation-proton antiporter , 1997, Journal of bacteriology.

[241]  M. Solioz,et al.  Purification and functional analysis of the copper ATPase CopA of Enterococcus hirae. , 2001, Biochemical and biophysical research communications.

[242]  T. Gilliam,et al.  Characterization of the Interaction between the Wilson and Menkes Disease Proteins and the Cytoplasmic Copper Chaperone, HAH1p* , 1999, The Journal of Biological Chemistry.

[243]  J. Ramos,et al.  A Set of Genes Encoding a Second Toluene Efflux System in Pseudomonas putida DOT-T1E Is Linked to the tod Genes for Toluene Metabolism , 2000, Journal of bacteriology.

[244]  M. Mergeay,et al.  Alcaligenes eutrophus CH34 is a facultative chemolithotroph with plasmid-bound resistance to heavy metals , 1985, Journal of bacteriology.

[245]  K. G. Coleman,et al.  Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. , 1997, Science.

[246]  Kendy K. Y. Wong,et al.  Insertion Mutagenesis and Membrane Topology Model of the Pseudomonas aeruginosa Outer Membrane Protein OprM , 2000, Journal of bacteriology.

[247]  R. Aono Improvement of organic solvent tolerance level of Escherichia coli by overexpression of stress-responsive genes. , 1998, Extremophiles : life under extreme conditions.

[248]  S. Karlin,et al.  Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[249]  M. Mergeay,et al.  Identification of a gene cluster, czr, involved in cadmium and zinc resistance in Pseudomonas aeruginosa. , 1999, Gene.

[250]  C. Rensing,et al.  CueO is a multi-copper oxidase that confers copper tolerance in Escherichia coli. , 2001, Biochemical and biophysical research communications.

[251]  T. Nakae,et al.  A novel assembly process of the multicomponent xenobiotic efflux pump in Pseudomonas aeruginosa , 2002, Molecular microbiology.

[252]  T. Steck,et al.  Circulation of Cholesterol between Lysosomes and the Plasma Membrane* , 1998, The Journal of Biological Chemistry.

[253]  B. Rosen,et al.  Biochemical Characterization of CopA, the Escherichia coli Cu(I)-translocating P-type ATPase* , 2002, The Journal of Biological Chemistry.

[254]  H. Schlegel,et al.  Combined nickel-cobalt-cadmium resistance encoded by the ncc locus of Alcaligenes xylosoxidans 31A , 1994, Journal of bacteriology.

[255]  T. Ohta,et al.  Chromosome‐Determined Zinc‐Responsible Operon czr in Staphylococcus aureus Strain 912 , 1999, Microbiology and immunology.

[256]  M. Dilworth,et al.  ActP controls copper homeostasis in Rhizobium leguminosarum bv. viciae and Sinorhizobium meliloti preventing low pH‐induced copper toxicity , 2002, Molecular microbiology.

[257]  F. Yoshimura,et al.  A Resistance-Nodulation-Cell Division Family Xenobiotic Efflux Pump in an Obligate Anaerobe, Porphyromonas gingivalis , 2002, Antimicrobial Agents and Chemotherapy.

[258]  Mami Yamamoto,et al.  Involvement of Outer Membrane Protein TolC, a Possible Member of the mar-sox Regulon, in Maintenance and Improvement of Organic Solvent Tolerance of Escherichia coli K-12 , 1998, Journal of bacteriology.

[259]  S. Silver,et al.  Mercury Resistance in a Plasmid-Bearing Strain of Escherichia coli , 1972, Journal of bacteriology.

[260]  C. Kado,et al.  An Isoflavonoid-Inducible Efflux Pump in Agrobacterium tumefaciens Is Involved in Competitive Colonization of Roots , 1998, Journal of bacteriology.

[261]  Juan L. Ramos,et al.  Efflux Pumps Involved in Toluene Tolerance in Pseudomonas putida DOT-T1E , 1998, Journal of bacteriology.

[262]  T. Nishino,et al.  Topological analysis of an RND family transporter, MexD of Pseudomonas aeruginosa , 1999, FEBS letters.

[263]  G. Perozzi,et al.  Cloning, expression, and vesicular localization of zinc transporter Dri 27/ZnT4 in intestinal tissue and cells. , 1999, American journal of physiology. Gastrointestinal and liver physiology.

[264]  C. Rensing,et al.  Families of Soft-Metal-Ion-Transporting ATPases , 1999, Journal of bacteriology.

[265]  D. Schüler,et al.  A Large Gene Cluster Encoding Several Magnetosome Proteins Is Conserved in Different Species of Magnetotactic Bacteria , 2001, Applied and Environmental Microbiology.

[266]  N. Brown,et al.  Chemical and Genetic Studies of Copper Resistance in E. coli , 1993 .

[267]  A. Michalczyk,et al.  Constitutive expression of hZnT4 zinc transporter in human breast epithelial cells. , 2002, The Biochemical journal.

[268]  L. Piddock,et al.  Identification and molecular characterisation of CmeB, a Campylobacter jejuni multidrug efflux pump. , 2002, FEMS microbiology letters.

[269]  T. Murata,et al.  On the mechanism of substrate specificity by resistance nodulation division (RND)‐type multidrug resistance pumps: the large periplasmic loops of MexD from Pseudomonas aeruginosa are involved in substrate recognition , 2002, Molecular microbiology.

[270]  P. Pentchev,et al.  Cholesterol reutilization during myelination of regenerating PNS axons is impaired in Niemann‐Pick disease type C mice , 1997, Journal of neuroscience research.

[271]  W. V. Shaw,et al.  Inducible plasmid-determined resistance to arsenate, arsenite, and antimony (III) in escherichia coli and Staphylococcus aureus , 1981, Journal of bacteriology.

[272]  S. Levy,et al.  Ineffectiveness of Topoisomerase Mutations in Mediating Clinically Significant Fluoroquinolone Resistance inEscherichia coli in the Absence of the AcrAB Efflux Pump , 2000, Antimicrobial Agents and Chemotherapy.

[273]  C. Rensing,et al.  Molecular Analysis of the Copper-Transporting Efflux System CusCFBA of Escherichia coli , 2003, Journal of bacteriology.

[274]  H. Loferer,et al.  Identification by RNA Profiling and Mutational Analysis of the Novel Copper Resistance Determinants CrdA (HP1326), CrdB (HP1327), and CzcB (HP1328) in Helicobacter pylori , 2002, Journal of bacteriology.

[275]  A. Kimura,et al.  Correlation of the OSR/ZRCI gene product and the intracellular glutathione levels in Saccharomyces cerevisiae , 1996, Biotechnology and applied biochemistry.

[276]  M. Nicholson,et al.  Genes encoded on a cyanobacterial plasmid are transcriptionally regulated by sulfur availability and CysR , 1995, Journal of bacteriology.

[277]  M H Saier,et al.  The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins. , 1999, Journal of molecular microbiology and biotechnology.

[278]  Y. Teranishi,et al.  Identification of a gene conferring resistance to zinc and cadmium ions in the yeast Saccharomyces cerevisiae , 1989, Molecular and General Genetics MGG.