Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria

Frontiers in Cellular and Infection Microbiology

Volumn 4, Issue OCT, 2013, Pages

  Troxell, Bryan ^a   Hassan, Hosni M ^b  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NORTH CAROLINA STATE UNIVERSITY   (United States)

Author keywords

Ferric uptake regulator; Gene regulation; Iron; Oxidative stress; Pathogenic bacteria

Indexed keywords

FERRIC ION; FERRIC UPTAKE REGULATOR; HYDROGEN PEROXIDE; MANGANESE; MANGANESE UPTAKE REGULATOR; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 1; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; RNA POLYMERASE; RNA POLYMERASE HOLOENZYME; RYHB; SIDEROPHORE; SUPEROXIDE DISMUTASE; UNCLASSIFIED DRUG; UNTRANSLATED RNA; ZINC UPTAKE REGULATOR; BACTERIAL PROTEIN; FERRIC UPTAKE REGULATING PROTEINS, BACTERIAL; REPRESSOR PROTEIN;

ARTICLE; BACTERIAL VIRULENCE; BACTERIUM; CHROMATIN IMMUNOPRECIPITATION; CITRIC ACID CYCLE; DEFENSE MECHANISM; DNA BINDING; FENTON REACTION; FTNA GENE; GENE; GENE ACTIVATION; GENE EXPRESSION; GENETIC REGULATION; GENETIC TRANSCRIPTION; HAEMOPHILUS INFLUENZAE; HOMEOSTASIS; HUMAN; LISTERIA MONOCYTOGENES; NONHUMAN; SALMONELLA ENTERICA; ANIMAL; BACTERIA; BACTERIAL INFECTION; GENE EXPRESSION REGULATION; GENETICS; HOST PATHOGEN INTERACTION; ISOLATION AND PURIFICATION; METABOLISM; MICROBIOLOGY; OXIDATIVE STRESS; TOXICITY;

ANIMALS; BACTERIA; BACTERIAL INFECTIONS; BACTERIAL PROTEINS; FERRIC COMPOUNDS; GENE EXPRESSION REGULATION, BACTERIAL; HOST-PATHOGEN INTERACTIONS; HUMANS; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; REPRESSOR PROTEINS; TRANSCRIPTION, GENETIC;

EID: 84896719872     PISSN: None     EISSN: 22352988     Source Type: Journal    
DOI: 10.3389/fcimb.2013.00059     Document Type: Article

References (222)

1. Afonyushkin, T., Vecerek, B., Moll, I., Blasi, U., and Kaberdin, V. R. (2005). Both RNase E and RNase III control the stability of sodB mRNA upon translational inhibition by the small regulatory RNA RyhB. Nucleic Acids Res. 33, 1678-1689. doi: 10.1093/nar/gki313
2. 2+ uptake system ZnuABC is required for bacterial zinc homeostasis in intracellular environments and contributes to the virulence of Salmonella enterica. Infect. Immun. 75, 5867-5876. doi: 10.1128/IAI.00559-07
3. Anderson, E. S., Paulley, J. T., Gaines, J. M., Valderas, M. W., Martin, D. W., Menscher, E., et al. (2009). The manganese transporter MntH is a critical virulence determinant for Brucella abortus 2308 in experimentally infected mice. Infect. Immun. 77, 3466-3474. doi: 10.1128/IAI.00444-09
4. Anjum, M. F., Stevanin, T. M., Read, R. C., and Moir, J. W. (2002). Nitric oxide metabolism in Neisseria meningitidis. J. Bacteriol. 184, 2987-2993. doi: 10.1128/JB.184.11.2987-2993.2002
5. Bagg, A., and Neilands, J. B. (1985). Mapping of a mutation affecting regulation of iron uptake systems in Escherichia coli K-12. J. Bacteriol. 161, 450-453.
6. Bagg, A., and Neilands, J. B. (1987a). Ferric uptake regulation protein acts as a repressor, employing iron (II) as a cofactor to bind the operator of an iron transport operon in Escherichia coli. Biochemistry 26, 5471-5477. doi: 10.1021/bi00391a039
7. Bagg, A., and Neilands, J. B. (1987b). Molecular mechanism of regulation of siderophore-mediated iron assimilation. Microbiol. Rev. 51, 509-518.
8. Baichoo, N., and Helmann, J. D. (2002). Recognition of DNA by Fur: a reinterpretation of the Fur box consensus sequence. J. Bacteriol. 184, 5826-5832. doi: 10.1128/JB.184.21.5826-5832.2002
9. Baumler, A. J., Tsolis, R. M., Van Der Velden, A. W., Stojiljkovic, I., Anic, S., and Heffron, F. (1996). Identification of a new iron regulated locus of Salmonella typhi. Gene 183, 207-213. doi: 10.1016/S0378-1119(96)00560-4
10. Beaumont, M. D., and Hassan, H. M. (1993). Characterization of regulatory mutations causing anaerobic derepression of the sodA gene in Escherichia coli K12: cooperation between cis- and trans-acting regulatory loci. J. Gen. Microbiol. 139, 2677-2684. doi: 10.1099/00221287-139-11-2677
11. Bellini, P., and Hemmings, A. M. (2006). In vitro characterization of a bacterial manganese uptake regulator of the fur superfamily. Biochemistry 45, 2686-2698. doi: 10.1021/bi052081n
12. Benov, L., and Sequeira, F. (2003). Escherichia coli deltafur mutant displays low HPII catalase activity in stationary phase. Redox Rep. 8, 379-383. doi: 10.1179/135100003225003357
13. Beraud, M., Kolb, A., Monteil, V., D'Alayer, J., and Norel, F. (2010). A proteomic analysis reveals differential regulation of the sigma(S)-dependent yciGFE(katN) locus by YncC and H-NS in Salmonella and Escherichia coli K-12. Mol. Cell. Proteomics 9, 2601-2616. doi: 10.1074/mcp.M110.002493
14. Bjarnason, J., Southward, C. M., and Surette, M. G. (2003). Genomic profiling of iron-responsive genes in Salmonella enterica serovar typhimurium by high-throughput screening of a random promoter library. J. Bacteriol. 185, 4973-4982. doi: 10.1128/JB.185.16.4973-4982.2003
15. Bourret, T. J., Porwollik, S., McClelland, M., Zhao, R., Greco, T., Ischiropoulos, H., et al. (2008). Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses. PLoS ONE 3:e1833. doi: 10.1371/journal.pone.0001833
16. Bowden, S. D., Ramachandran, V. K., Knudsen, G. M., Hinton, J. C., and Thompson, A. (2010). An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages. PLoS ONE 5:e13871. doi: 10.1371/journal.pone.0013871
17. Boyer, E., Bergevin, I., Malo, D., Gros, P., and Cellier, M. F. (2002). Acquisition of Mn(II) in addition to Fe(II) is required for full virulence of Salmonella enterica serovar Typhimurium. Infect. Immun. 70, 6032-6042. doi: 10.1128/IAI.70.11.6032-6042.2002
18. Bradley, D. J. (1977). Regulation of Leishmania populations within the host. II. genetic control of acute susceptibility of mice to Leishmania donovani infection. Clin. Exp. Immunol. 30, 130-140.
19. Brickman, T. J., Ozenberger, B. A., and McIntosh, M. A. (1990). Regulation of divergent transcription from the iron-responsive fepB-entC promoter-operator regions in Escherichia coli. J. Mol. Biol. 212, 669-682. doi: 10.1016/0022-2836(90)90229-F
20. Brot, N., and Goodwin, J. (1968). Regulation of 2,3-dihydroxybenzoylserine synthetase by iron. J. Biol. Chem. 243, 510-513.
21. Brown, D. E., Libby, S. J., Moreland, S. M., McCoy, M. W., Brabb, T., Stepanek, A., et al. (2013). Salmonella enterica Causes more severe inflammatory disease in C57/BL6 Nramp1G169 Mice Than Sv129S6 Mice. Vet. Pathol. 50, 867-876. doi: 10.1177/0300985813478213
22. Bryce, G. F., and Brot, N. (1971). Iron transport in Escherichia coli and its relation to the repression of 2,3-dihydroxy-N-benzoyl-L-serine synthetase. Arch. Biochem. Biophys. 142, 399-406. doi: 10.1016/0003-9861(71)90503-0
23. Bsat, N., Herbig, A., Casillas-Martinez, L., Setlow, P., and Helmann, J. D. (1998). Bacillus subtilis contains multiple Fur homologues: identification of the iron uptake (Fur) and peroxide regulon (PerR) repressors. Mol. Microbiol. 29, 189-198. doi: 10.1046/j.1365-2958.1998.00921.x
24. Bury-Mone, S., Thiberge, J. M., Contreras, M., Maitournam, A., Labigne, A., and De Reuse, H. (2004). Responsiveness to acidity via metal ion regulators mediates virulence in the gastric pathogen Helicobacter pylori. Mol. Microbiol. 53, 623-638. doi: 10.1111/j.1365-2958.2004.04137.x
25. Busby, S., and Ebright, R. H. (1994). Promoter structure, promoter recognition, and transcription activation in prokaryotes. Cell 79, 743-746. doi: 10.1016/0092-8674(94)90063-9
26. Calderwood, S. B., and Mekalanos, J. J. (1987). Iron regulation of Shiga-like toxin expression in Escherichia coli is mediated by the fur locus. J. Bacteriol. 169, 4759-4764.
27. Calderwood, S. B., and Mekalanos, J. J. (1988). Confirmation of the Fur operator site by insertion of a synthetic oligonucleotide into an operon fusion plasmid. J. Bacteriol. 170, 1015-1017.
28. Campoy, S., Jara, M., Busquets, N., Perez De Rozas, A. M., Badiola, I., and Barbe, J. (2002). Role of the high-affinity zinc uptake znuABC system in Salmonella enterica serovar typhimurium virulence. Infect. Immun. 70, 4721-4725. doi: 10.1128/IAI.70.8.4721-4725.2002
29. Canonne-Hergaux, F., Calafat, J., Richer, E., Cellier, M., Grinstein, S., Borregaard, N., et al. (2002). Expression and subcellular localization of NRAMP1 in human neutrophil granules. Blood 100, 268-275. doi: 10.1182/blood.V100.1.268
30. Carpenter, B. M., Whitmire, J. M., and Merrell, D. S. (2009). This is not your mother's repressor: the complex role of fur in pathogenesis. Infect. Immun. 77, 2590-2601. doi: 10.1128/IAI.00116-09
31. Cartwright, G. E., Lauritsen, M. A., Jones, P. J., Merrill, I. M., and Wintrobe, M. M. (1946). The anemia of infection. i. hypoferremia, hypercupremia, and alterations in porphyrin metabolism in patients. J. Clin. Invest. 25, 65-80. doi: 10.1172/JCI101690
32. Cellier, M., Prive, G., Belouchi, A., Kwan, T., Rodrigues, V., Chia, W., et al. (1995). Nramp defines a family of membrane proteins. Proc. Natl. Acad. Sci. U.S.A. 92, 10089-10093. doi: 10.1073/pnas.92.22.10089
33. Cellier, M. F. (2012). Nramp: from sequence to structure and mechanism of divalent metal import. Curr. Top. Membr. 69, 249-293. doi: 10.1016/B978-0-12-394390-3.00010-0
34. Champion, O. L., Karlyshev, A., Cooper, I. A., Ford, D. C., Wren, B. W., Duffield, M., et al. (2011). Yersinia pseudotuberculosis mntH functions in intracellular manganese accumulation, which is essential for virulence and survival in cells expressing functional Nramp1. Microbiology 157, 1115-1122. doi: 10.1099/mic.0.045807-0
35. Claiborne, A., and Fridovich, I. (1979). Purification of the o-dianisidine peroxidase from Escherichia coli B. Physicochemical characterization and analysis of its dual catalatic and peroxidatic activities. J. Biol. Chem. 254, 4245-4252.
36. Claiborne, A., Malinowski, D. P., and Fridovich, I. (1979). Purification and characterization of hydroperoxidase II of Escherichia coli B. J. Biol. Chem. 254, 11664-11668.
37. Corbett, D., Wang, J., Schuler, S., Lopez-Castejon, G., Glenn, S., Brough, D., et al. (2012). Two zinc uptake systems contribute to the full virulence of Listeria monocytogenes during growth in vitro and in vivo. Infect. Immun. 80, 14-21. doi: 10.1128/IAI.05904-11
38. Corbin, B. D., Seeley, E. H., Raab, A., Feldmann, J., Miller, M. R., Torres, V. J., et al. (2008). Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319, 962-965. doi: 10.1126/science.1152449
39. Cosgrove, K., Coutts, G., Jonsson, I. M., Tarkowski, A., Kokai-Kun, J. F., Mond, J. J., et al. (2007). Catalase (KatA) and alkyl hydroperoxide reductase (AhpC) have compensatory roles in peroxide stress resistance and are required for survival, persistence, and nasal colonization in Staphylococcus aureus. J. Bacteriol. 189, 1025-1035. doi: 10.1128/JB.01524-06
40. Craig, S. A., Carpenter, C. D., Mey, A. R., Wyckoff, E. E., and Payne, S. M. (2011). Positive regulation of the Vibrio cholerae porin OmpT by iron and fur. J. Bacteriol. 193, 6505-6511. doi: 10.1128/JB.05681-11
41. Curtiss, R. 3rd. Wanda, S. Y., Gunn, B. M., Zhang, X., Tinge, S. A., Ananthnarayan, V., et al. (2009). Salmonella enterica serovar typhimurium strains with regulated delayed attenuation in vivo. Infect. Immun. 77, 1071-1082. doi: 10.1128/IAI.00693-08
42. Damo, S. M., Kehl-Fie, T. E., Sugitani, N., Holt, M. E., Rathi, S., Murphy, W. J., et al. (2013). Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens. Proc. Natl. Acad. Sci. U.S.A. 110, 3841-3846. doi: 10.1073/pnas.1220341110
43. D'Autreaux, B., Touati, D., Bersch, B., Latour, J. M., and Michaud-Soret, I. (2002). Direct inhibition by nitric oxide of the transcriptional ferric uptake regulation protein via nitrosylation of the iron. Proc. Natl. Acad. Sci. U.S.A. 99, 16619-16624. doi: 10.1073/pnas.252591299
44. Davis, B. M., Quinones, M., Pratt, J., Ding, Y., and Waldor, M. K. (2005). Characterization of the small untranslated RNA RyhB and its regulon in Vibrio cholerae. J. Bacteriol. 187, 4005-4014. doi: 10.1128/JB.187.12.4005-4014.2005
45. De Lorenzo, V., Wee, S., Herrero, M., and Neilands, J. B. (1987). Operator sequences of the aerobactin operon of plasmid ColV-K30 binding the ferric uptake regulation (fur) repressor. J. Bacteriol. 169, 2624-2630.
46. Defez, R., and De Felice, M. (1981). Cryptic operon for beta-glucoside metabolism in Escherichia coli K12: genetic evidence for a regulatory protein. Genetics 97, 11-25.
47. Delany, I., Pacheco, A. B., Spohn, G., Rappuoli, R., and Scarlato, V. (2001). Iron-dependent transcription of the frpB gene of Helicobacter pylori is controlled by the Fur repressor protein. J. Bacteriol. 183, 4932-4937. doi: 10.1128/JB.183.16.4932-4937.2001
48. Delany, I., Rappuoli, R., and Scarlato, V. (2004). Fur functions as an activator and as a repressor of putative virulence genes in Neisseria meningitidis. Mol. Microbiol. 52, 1081-1090. doi: 10.1111/j.1365-2958.2004.04030.x
49. Deng, Z., Meng, X., Su, S., Liu, Z., Ji, X., Zhang, Y., et al. (2012). Two sRNA RyhB homologs from Yersinia pestis biovar microtus expressed in vivo have differential Hfq-dependent stability. Res. Microbiol. 163, 413-418. doi: 10.1016/j.resmic.2012.05.006
50. Desrosiers, D. C., Bearden, S. W., Mier, I. Jr. Abney, J., Paulley, J. T., Fetherston, J. D., et al. (2010). Znu is the predominant zinc importer in Yersinia pestis during in vitro growth but is not essential for virulence. Infect. Immun. 78, 5163-5177. doi: 10.1128/IAI.00732-10
51. 2+ )-responsive transcriptional regulator. Microbiology 150, 1447-1456. doi: 10.1099/mic.0.26961-0
52. Diaz-Mireles, E., Wexler, M., Todd, J. D., Bellini, D., Johnston, A. W., and Sawers, R. G. (2005). The manganese-responsive repressor Mur of Rhizobium leguminosarum is a member of the Fur-superfamily that recognizes an unusual operator sequence. Microbiology 151, 4071-4078. doi: 10.1099/mic.0.28342-0
53. Dlaska, M., and Weiss, G. (1999). Central role of transcription factor NF-IL6 for cytokine and iron-mediated regulation of murine inducible nitric oxide synthase expression. J. Immunol. 162, 6171-6177.
54. Dowd, G. C., Casey, P. G., Begley, M., Hill, C., and Gahan, C. G. (2012). Investigation of the role of ZurR in the physiology and pathogenesis of Listeria monocytogenes. FEMS Microbiol. Lett. 327, 118-125. doi: 10.1111/j.1574-6968.2011.02472.x
55. Drakesmith, H., and Prentice, A. M. (2012). Hepcidin and the iron-infection axis. Science 338, 768-772. doi: 10.1126/science.1224577
56. Dubrac, S., and Touati, D. (2000). Fur positive regulation of iron superoxide dismutase in Escherichia coli: functional analysis of the sodB promoter. J. Bacteriol. 182, 3802-3808. doi: 10.1128/JB.182.13.3802-3808.2000
57. Dubrac, S., and Touati, D. (2002). Fur-mediated transcriptional and post-transcriptional regulation of FeSOD expression in Escherichia coli. Microbiology 148, 147-156.
58. Ducey, T. F., Jackson, L., Orvis, J., and Dyer, D. W. (2009). Transcript analysis of nrrF, a Fur repressed sRNA of Neisseria gonorrhoeae. Microb. Pathog. 46, 166-170. doi: 10.1016/j.micpath.2008.12.003
59. Ebanks, R. O., Goguen, M., Knickle, L., Dacanay, A., Leslie, A., Ross, N. W., et al. (2013). Analysis of a ferric uptake regulator (Fur) knockout mutant in Aeromonas salmonicida subsp. salmonicida. Vet. Microbiol. 162, 831-841. doi: 10.1016/j.vetmic.2012.10.038
60. Ebright, R. H., and Busby, S. (1995). The Escherichia coli RNA polymerase alpha subunit: structure and function. Curr. Opin. Genet. Dev. 5, 197-203. doi: 10.1016/0959-437X(95)80008-5
61. Ellermeier, C. D., Ellermeier, J. R., and Slauch, J. M. (2005). HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium. Mol. Microbiol. 57, 691-705. doi: 10.1111/j.1365-2958.2005.04737.x
62. Ellermeier, J. R., and Slauch, J. M. (2008). Fur regulates expression of the Salmonella pathogenicity island 1 type III secretion system through HilD. J. Bacteriol. 190, 476-486. doi: 10.1128/JB.00926-07
63. Ernst, J. F., Bennett, R. L., and Rothfield, L. I. (1978). Constitutive expression of the iron-enterochelin and ferrichrome uptake systems in a mutant strain of Salmonella typhimurium. J. Bacteriol. 135, 928-934.
64. Escolar, L., De Lorenzo, V., and Perez-Martin, J. (1997). Metalloregulation in vitro of the aerobactin promoter of Escherichia coli by the Fur (ferric uptake regulation) protein. Mol. Microbiol. 26, 799-808. doi: 10.1046/j.1365-2958.1997.6211987.x
65. Escolar, L., Perez-Martin, J., and De Lorenzo, V. (1998). Coordinated repression in vitro of the divergent fepA-fes promoters of Escherichia coli by the iron uptake regulation (Fur) protein. J. Bacteriol. 180, 2579-2582.
66. Escolar, L., Perez-Martin, J., and De Lorenzo, V. (1999). Opening the iron box: transcriptional metalloregulation by the Fur protein. J. Bacteriol. 181, 6223-6229.
67. Escolar, L., Perez-Martin, J., and De Lorenzo, V. (2000). Evidence of an unusually long operator for the fur repressor in the aerobactin promoter of Escherichia coli. J. Biol. Chem. 275, 24709-24714. doi: 10.1074/jbc.M002839200
68. Fassbinder, F., Van Vliet, A. H., Gimmel, V., Kusters, J. G., Kist, M., and Bereswill, S. (2000). Identification of iron-regulated genes of Helicobacter pylori by a modified fur titration assay (FURTA-Hp). FEMS Microbiol. Lett. 184, 225-229. doi: 10.1111/j.1574-6968.2000.tb09018.x
69. Fenton, H. (1894). Oxidation of tartaric acid in presence of iron. J. Chem. Soc. Trans. 65, 899-911. doi: 10.1039/ct8946500899
70. Fleischhacker, A. S., and Kiley, P. J. (2011). Iron-containing transcription factors and their roles as sensors. Curr. Opin. Chem. Biol. 15, 335-341. doi: 10.1016/j.cbpa.2011.01.006
71. Forbes, J. R., and Gros, P. (2003). Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood 102, 1884-1892. doi: 10.1182/blood-2003-02-0425
72. Foster, J. W., and Hall, H. K. (1992). Effect of Salmonella typhimurium ferric uptake regulator (fur) mutations on iron- and pH-regulated protein synthesis. J. Bacteriol. 174, 4317-4323.
73. Fritsche, G., Dlaska, M., Barton, H., Theurl, I., Garimorth, K., and Weiss, G. (2003). Nramp1 functionality increases inducible nitric oxide synthase transcription via stimulation of IFN regulatory factor 1 expression. J. Immunol. 171, 1994-1998.
74. Fritsche, G., Nairz, M., Libby, S. J., Fang, F. C., and Weiss, G. (2012). Slc11a1 (Nramp1) impairs growth of Salmonella enterica serovar typhimurium in macrophages via stimulation of lipocalin-2 expression. J. Leukoc. Biol. 92, 353-359. doi: 10.1189/jlb.1111554
75. Fritsche, G., Nairz, M., Werner, E. R., Barton, H. C., and Weiss, G. (2008). Nramp1-functionality increases iNOS expression via repression of IL-10 formation. Eur. J. Immunol. 38, 3060-3067. doi: 10.1002/eji.200838449
76. Gaballa, A., and Helmann, J. D. (1998). Identification of a zinc-specific metalloregulatory protein, Zur, controlling zinc transport operons in Bacillus subtilis. J. Bacteriol. 180, 5815-5821.
77. Gaballa, A., and Helmann, J. D. (2002). A peroxide-induced zinc uptake system plays an important role in protection against oxidative stress in Bacillus subtilis. Mol. Microbiol. 45, 997-1005. doi: 10.1046/j.1365-2958.2002.03068.x
78. Gaballa, A., Antelmann, H., Aguilar, C., Khakh, S. K., Song, K. B., Smaldone, G. T., et al. (2008). The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins. Proc. Natl. Acad. Sci. U.S.A. 105, 11927-11932. doi: 10.1073/pnas.0711752105
79. Gabriel, S. E., and Helmann, J. D. (2009). Contributions of Zur-controlled ribosomal proteins to growth under zinc starvation conditions. J. Bacteriol. 191, 6116-6122. doi: 10.1128/JB.00802-09
80. Gancz, H., Censini, S., and Merrell, D. S. (2006). Iron and pH homeostasis intersect at the level of Fur regulation in the gastric pathogen Helicobacter pylori. Infect. Immun. 74, 602-614. doi: 10.1128/IAI.74.1.602-614.2006
81. Gehring, A. M., Mori, I., and Walsh, C. T. (1998). Reconstitution and characterization of the Escherichia coli enterobactin synthetase from EntB, EntE, and EntF. Biochemistry 37, 2648-2659. doi: 10.1021/bi9726584
82. Gielda, L. M., and Dirita, V. J. (2012). Zinc competition among the intestinal microbiota. MBio 3, e00171-12. doi: 10.1128/mBio.00171-12
83. Gilbreath, J. J., West, A. L., Pich, O. Q., Carpenter, B. M., Michel, S., and Merrell, D. S. (2012). Fur activates expression of the 2-oxoglutarate oxidoreductase genes (oorDABC) in Helicobacter pylori. J. Bacteriol. 194, 6490-6497. doi: 10.1128/JB.01226-12
84. Greenberg, G. R., Ashenbrucker, H., Lauritsen, M., Worth, W., Humphreys, S. R., and Wintrobe, M. M. (1947). The anemia of infection. V. fate of injected radioactive iron in the presence of inflammation. J. Clin. Invest. 26, 121-125. doi: 10.1172/JCI101784
85. Gruer, M. J., and Guest, J. R. (1994). Two genetically-distinct and differentially-regulated aconitases (AcnA and AcnB) in Escherichia coli. Microbiology 140(Pt 10), 2531-2541. doi: 10.1099/00221287-140-10-2531
86. Gryllos, I., Grifantini, R., Colaprico, A., Cary, M. E., Hakansson, A., Carey, D. W., et al. (2008). PerR confers phagocytic killing resistance and allows pharyngeal colonization by group A Streptococcus. PLoS Pathog. 4:e1000145. doi: 10.1371/journal.ppat.1000145
87. Guedon, E., Moore, C. M., Que, Q., Wang, T., Ye, R. W., and Helmann, J. D. (2003). The global transcriptional response of Bacillus subtilis to manganese involves the MntR, Fur, TnrA and sigmaB regulons. Mol. Microbiol. 49, 1477-1491. doi: 10.1046/j.1365-2958.2003.03648.x
88. Hackam, D. J., Rotstein, O. D., Zhang, W., Gruenheid, S., Gros, P., and Grinstein, S. (1998). Host resistance to intracellular infection: mutation of natural resistance-associated macrophage protein 1 (Nramp1) impairs phagosomal acidification. J. Exp. Med. 188, 351-364. doi: 10.1084/jem.188.2.351
89. Hamza, I., Qi, Z., King, N. D., and O'Brian, M. R. (2000). Fur-independent regulation of iron metabolism by Irr in Bradyrhizobium japonicum. Microbiology 146(Pt 3), 669-676.
90. Hantke, K. (1981). Regulation of ferric iron transport in Escherichia coli K12: isolation of a constitutive mutant. Mol. Gen. Genet. 182, 288-292. doi: 10.1007/BF00269672
91. Hantke, K. (1983). Identification of an iron uptake system specific for coprogen and rhodotorulic acid in Escherichia coli K12. Mol. Gen. Genet. 191, 301-306. doi: 10.1007/BF00334830
92. Hantke, K. (1984). Cloning of the repressor protein gene of iron-regulated systems in Escherichia coli K12. Mol. Gen. Genet. 197, 337-341. doi: 10.1007/BF00330982
93. Hantke, K. (1987). Selection procedure for deregulated iron transport mutants (fur) in Escherichia coli K 12: fur not only affects iron metabolism. Mol. Gen. Genet. 210, 135-139. doi: 10.1007/BF00337769
94. Hantke, K. (2001). Iron and metal regulation in bacteria. Curr. Opin. Microbiol. 4, 172-177. doi: 10.1016/S1369-5274(00)00184-3
95. Haraszthy, V. I., Jordan, S. F., and Zambon, J. J. (2006). Identification of Fur-regulated genes in Actinobacillus actinomycetemcomitans. Microbiology 152, 787-796. doi: 10.1099/mic.0.28366-0
96. Harrison, A., Santana, E. A., Szelestey, B. R., Newsom, D. E., White, P., and Mason, K. M. (2013). Ferric uptake regulator and its role in the pathogenesis of nontypeable Haemophilus influenzae. Infect. Immun. 81, 1221-1233. doi: 10.1128/IAI.01227-12
97. Hassan, H. M., and Fridovich, I. (1978). Regulation of the synthesis of catalase and peroxidase in Escherichia coli. J. Biol. Chem. 253, 6445-6420.
98. Hassan, H. M., and Schrum, L. W. (1994). Roles of manganese and iron in the regulation of the biosynthesis of manganese-superoxide dismutase in Escherichia coli. FEMS Microbiol. Rev. 14, 315-323. doi: 10.1111/j.1574-6976.1994.tb00105.x
99. Hebrard, M., Viala, J. P., Meresse, S., Barras, F., and Aussel, L. (2009). Redundant hydrogen peroxide scavengers contribute to Salmonella virulence and oxidative stress resistance. J. Bacteriol. 191, 4605-4614. doi: 10.1128/JB.00144-09
100. Herbig, A. F., and Helmann, J. D. (2001). Roles of metal ions and hydrogen peroxide in modulating the interaction of theBacillus subtilis PerR peroxide regulon repressor with operator DNA. Mol. Microbiol. 41, 849-859. doi: 10.1046/j.1365-2958.2001.02543.x
101. Hochschild, A., and Dove, S. L. (1998). Protein-protein contacts that activate and repress prokaryotic transcription. Cell 92, 597-600. doi: 10.1016/S0092-8674(00)81126-5
102. Hoerter, J. D., Arnold, A. A., Ward, C. S., Sauer, M., Johnson, S., Fleming, T., et al. (2005). Reduced hydroperoxidase (HPI and HPII) activity in the Deltafur mutant contributes to increased sensitivity to UVA radiation in Escherichia coli. J. Photochem. Photobiol. B. 79, 151-157. doi: 10.1016/j.jphotobiol.2005.01.003
103. Hood, M. I., and Skaar, E. P. (2012). Nutritional immunity: transition metals at the pathogen-host interface. Nat. Rev. Microbiol. 10, 525-537. doi: 10.1038/nrmicro2836
104. Horsburgh, M. J., Clements, M. O., Crossley, H., Ingham, E., and Foster, S. J. (2001a). PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. Infect. Immun. 69, 3744-3754. doi: 10.1128/IAI.69.6.3744-3754.2001
105. Horsburgh, M. J., Ingham, E., and Foster, S. J. (2001b). In Staphylococcus aureus, fur is an interactive regulator with PerR, contributes to virulence, and Is necessary for oxidative stress resistance through positive regulation of catalase and iron homeostasis. J. Bacteriol. 183, 468-475. doi: 10.1128/JB.183.2.468-475.2001
106. Horst, S. A., Jaeger, T., Denkel, L. A., Rouf, S. F., Rhen, M., and Bange, F. C. (2010). Thiol peroxidase protects Salmonella enterica from hydrogen peroxide stress in vitro and facilitates intracellular growth. J. Bacteriol. 192, 2929-2932. doi: 10.1128/JB.01652-09
107. Huang, S. H., Wang, C. K., Peng, H. L., Wu, C. C., Chen, Y. T., Hong, Y. M., et al. (2012). Role of the small RNA RyhB in the Fur regulon in mediating the capsular polysaccharide biosynthesis and iron acquisition systems in Klebsiella pneumoniae. BMC Microbiol. 12:148. doi: 10.1186/1471-2180-12-148
108. Hughes, N. J., Clayton, C. L., Chalk, P. A., and Kelly, D. J. (1998). Helicobacter pylori porCDAB and oorDABC genes encode distinct pyruvate:flavodoxin and 2-oxoglutarate:acceptor oxidoreductases which mediate electron transport to NADP. J. Bacteriol. 180, 1119-1128.
109. Ikeda, J. S., Janakiraman, A., Kehres, D. G., Maguire, M. E., and Slauch, J. M. (2005). Transcriptional regulation of sitABCD of Salmonella enterica serovar Typhimurium by MntR and Fur. J. Bacteriol. 187, 912-922. doi: 10.1128/JB.187.3.912-922.2005
110. Imlay, J. A., Chin, S. M., and Linn, S. (1988). Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 240, 640-642. doi: 10.1126/science.2834821
111. Isabella, V., Wright, L. F., Barth, K., Spence, J. M., Grogan, S., Genco, C. A., et al. (2008). cis- and trans-acting elements involved in regulation of norB (norZ), the gene encoding nitric oxide reductase in Neisseria gonorrhoeae. Microbiology 154, 226-239. doi: 10.1099/mic.0.2007/010470-0
112. Ishihama, A. (1992). Role of the RNA polymerase alpha subunit in transcription activation. Mol. Microbiol. 6, 3283-3288. doi: 10.1111/j.1365-2958.1992.tb02196.x
113. Ivanova, A., Miller, C., Glinsky, G., and Eisenstark, A. (1994). Role of rpoS (katF) in oxyR-independent regulation of hydroperoxidase I in Escherichia coli. Mol. Microbiol. 12, 571-578. doi: 10.1111/j.1365-2958.1994.tb01043.x
114. Jabado, N., Jankowski, A., Dougaparsad, S., Picard, V., Grinstein, S., and Gros, P. (2000). Natural resistance to intracellular infections: natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J. Exp. Med. 192, 1237-1248. doi: 10.1084/jem.192.9.1237
115. Jackson, L. A., Ducey, T. F., Day, M. W., Zaitshik, J. B., Orvis, J., and Dyer, D. W. (2010). Transcriptional and functional analysis of the Neisseria gonorrhoeae Fur regulon. J. Bacteriol. 192, 77-85. doi: 10.1128/JB.00741-09
116. Jacobsen, I., Gerstenberger, J., Gruber, A. D., Bosse, J. T., Langford, P. R., Hennig-Pauka, I., et al. (2005). Deletion of the ferric uptake regulator Fur impairs the in vitro growth and virulence of Actinobacillus pleuropneumoniae. Infect. Immun. 73, 3740-3744. doi: 10.1128/IAI.73.6.3740-3744.2005
117. Jacques, J. F., Jang, S., Prevost, K., Desnoyers, G., Desmarais, M., Imlay, J., et al. (2006). RyhB small RNA modulates the free intracellular iron pool and is essential for normal growth during iron limitation in Escherichia coli. Mol. Microbiol. 62, 1181-1190. doi: 10.1111/j.1365-2958.2006.05439.x
118. Keele, B. B. Jr. McCord, J. M., and Fridovich, I. (1970). Superoxide dismutase from Escherichia coli B. A new manganese-containing enzyme. J. Biol. Chem. 245, 6176-6181.
119. Kehl-Fie, T. E., Chitayat, S., Hood, M. I., Damo, S., Restrepo, N., Garcia, C., et al. (2011). Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. Cell Host Microbe 10, 158-164. doi: 10.1016/j.chom.2011.07.004
120. Kehl-Fie, T. E., and Skaar, E. P. (2010). Nutritional immunity beyond iron: a role for manganese and zinc. Curr. Opin. Chem. Biol. 14, 218-224. doi: 10.1016/j.cbpa.2009.11.008
121. 2+ ). J. Bacteriol. 184, 3151-3158. doi: 10.1128/JB.184.12.3151-3158.2002
122. Kim, J. N., and Kwon, Y. M. (2013). Genetic and phenotypic characterization of the RyhB regulon in Salmonella Typhimurium. Microbiol. Res. 168, 41-49. doi: 10.1016/j.micres.2012.06.007
123. Kluger, M. J., and Rothenburg, B. A. (1979). Fever and reduced iron: their interaction as a host defense response to bacterial infection. Science 203, 374-376. doi: 10.1126/science.760197
124. Lafont, J. P., Dho, M., D'Hauteville, H. M., Bree, A., and Sansonetti, P. J. (1987). Presence and expression of aerobactin genes in virulent avian strains of Escherichia coli. Infect. Immun. 55, 193-197.
125. Lavrrar, J. L., Christoffersen, C. A., and McIntosh, M. A. (2002). Fur-DNA interactions at the bidirectional fepDGC-entS promoter region in Escherichia coli. J. Mol. Biol. 322, 983-995. doi: 10.1016/S0022-2836(02)00849-5
126. Leclerc, J. M., Dozois, C. M., and Daigle, F. (2013). Role of the Salmonella enterica serovar Typhi Fur regulator and small RNAs RfrA and RfrB in iron homeostasis and interaction with host cells. Microbiology 159, 591-602. doi: 10.1099/mic.0.064329-0
127. Lee, H. J., Kim, J. A., Lee, M. A., Park, S. J., and Lee, K. H. (2013). Regulation of haemolysin (VvhA) production by ferric uptake regulator (Fur) in Vibrio vulnificus: repression of vvhA transcription by Fur and proteolysis of VvhA by Fur-repressive exoproteases. Mol. Microbiol. 88, 813-826. doi: 10.1111/mmi.12224
128. Lee, J. W., and Helmann, J. D. (2006). The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation. Nature 440, 363-367. doi: 10.1038/nature04537
129. Lee, J. W., and Helmann, J. D. (2007). Functional specialization within the Fur family of metalloregulators. Biometals 20, 485-499. doi: 10.1007/s10534-006-9070-7
130. Lindgren, H., Shen, H., Zingmark, C., Golovliov, I., Conlan, W., and Sjostedt, A. (2007). Resistance of Francisella tularensis strains against reactive nitrogen and oxygen species with special reference to the role of KatG. Infect. Immun. 75, 1303-1309. doi: 10.1128/IAI.01717-06
131. Ling, J., Pan, H., Gao, Q., Xiong, L., Zhou, Y., Zhang, D., et al. (2013). Aerobactin synthesis genes iucA and iucC contribute to the pathogenicity of avian pathogenic Escherichia coli O2 strain E058. PLoS ONE 8:e57794. doi: 10.1371/journal.pone.0057794
132. Lloyd, R. V., Hanna, P. M., and Mason, R. P. (1997). The origin of the hydroxyl radical oxygen in the Fenton reaction. Free Radic. Biol. Med. 22, 885-888. doi: 10.1016/S0891-5849(96)00432-7
133. Maciag, A., Dainese, E., Rodriguez, G. M., Milano, A., Provvedi, R., Pasca, M. R., et al. (2007). Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon. J. Bacteriol. 189, 730-740. doi: 10.1128/JB.01190-06
134. Masse, E., and Gottesman, S. (2002). A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 99, 4620-4625. doi: 10.1073/pnas.032066599
135. Masse, E., Vanderpool, C. K., and Gottesman, S. (2005). Effect of RyhB small RNA on global iron use in Escherichia coli. J. Bacteriol. 187, 6962-6971. doi: 10.1128/JB.187.20.6962-6971.2005
136. May, G., Dersch, P., Haardt, M., Middendorf, A., and Bremer, E. (1990). The osmZ (bglY) gene encodes the DNA-binding protein H-NS (H1a), a component of the Escherichia coli K12 nucleoid. Mol. Gen. Genet. 224, 81-90. doi: 10.1007/BF00259454
137. McHugh, J. P., Rodriguez-Quinones, F., Abdul-Tehrani, H., Svistunenko, D. A., Poole, R. K., Cooper, C. E., et al. (2003). Global iron-dependent gene regulation in Escherichia coli. A new mechanism for iron homeostasis. J. Biol. Chem. 278, 29478-29486. doi: 10.1074/jbc.M303381200
138. Melillo, G., Taylor, L. S., Brooks, A., Musso, T., Cox, G. W., and Varesio, L. (1997). Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promoter by the iron chelator desferrioxamine. J. Biol. Chem. 272, 12236-12243. doi: 10.1074/jbc.272.18.12236
139. Mellin, J. R., Goswami, S., Grogan, S., Tjaden, B., and Genco, C. A. (2007). A novel fur- and iron-regulated small RNA, NrrF, is required for indirect fur-mediated regulation of the sdhA and sdhC genes in Neisseria meningitidis. J. Bacteriol. 189, 3686-3694. doi: 10.1128/JB.01890-06
140. Menscher, E. A., Caswell, C. C., Anderson, E. S., and Roop, R. M. 2nd. (2012). Mur regulates the gene encoding the manganese transporter MntH in Brucella abortus 2308. J. Bacteriol. 194, 561-566. doi: 10.1128/JB.05296-11
141. Metruccio, M. M., Fantappie, L., Serruto, D., Muzzi, A., Roncarati, D., Donati, C., et al. (2009). The Hfq-dependent small noncoding RNA NrrF directly mediates Fur-dependent positive regulation of succinate dehydrogenase in Neisseria meningitidis. J. Bacteriol. 191, 1330-1342. doi: 10.1128/JB.00849-08
142. Mey, A. R., Craig, S. A., and Payne, S. M. (2005a). Characterization of Vibrio cholerae RyhB: the RyhB regulon and role of ryhB in biofilm formation. Infect. Immun. 73, 5706-5719. doi: 10.1128/IAI.73.9.5706-5719.2005
143. Mey, A. R., Wyckoff, E. E., Kanukurthy, V., Fisher, C. R., and Payne, S. M. (2005b). Iron and fur regulation in Vibrio cholerae and the role of fur in virulence. Infect. Immun. 73, 8167-8178. doi: 10.1128/IAI.73.12.8167-8178.2005
144. Minato, Y., Fassio, S. R., Wolfe, A. J., and Hase, C. C. (2013). Central metabolism controls transcription of a virulence gene regulator in Vibrio cholerae. Microbiology 159, 792-802. doi: 10.1099/mic.0.064865-0
145. Mongkolsuk, S., and Helmann, J. D. (2002). Regulation of inducible peroxide stress responses. Mol. Microbiol. 45, 9-15. doi: 10.1046/j.1365-2958.2002.03015.x
146. Mukhopadhyay, P., Zheng, M., Bedzyk, L. A., Larossa, R. A., and Storz, G. (2004). Prominent roles of the NorR and Fur regulators in the Escherichia coli transcriptional response to reactive nitrogen species. Proc. Natl. Acad. Sci. U.S.A. 101, 745-750. doi: 10.1073/pnas.0307741100
147. Murakami, K., Owens, J. T., Belyaeva, T. A., Meares, C. F., Busby, S. J., and Ishihama, A. (1997). Positioning of two alpha subunit carboxy-terminal domains of RNA polymerase at promoters by two transcription factors. Proc. Natl. Acad. Sci. U.S.A. 94, 11274-11278. doi: 10.1073/pnas.94.21.11274
148. Murphy, E. R., and Payne, S. M. (2007). RyhB, an iron-responsive small RNA molecule, regulates Shigella dysenteriae virulence. Infect. Immun. 75, 3470-3477. doi: 10.1128/IAI.00112-07
149. Nairz, M., Fritsche, G., Crouch, M. L., Barton, H. C., Fang, F. C., and Weiss, G. (2009). Slc11a1 limits intracellular growth of Salmonella enterica sv. Typhimurium by promoting macrophage immune effector functions and impairing bacterial iron acquisition. Cell. Microbiol. 11, 1365-1381. doi: 10.1111/j.1462-5822.2009.01337.x
150. Nairz, M., Schleicher, U., Schroll, A., Sonnweber, T., Theurl, I., Ludwiczek, S., et al. (2013). Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection. J. Exp. Med. 210, 855-873. doi: 10.1084/jem.20121946
151. Nairz, M., Theurl, I., Ludwiczek, S., Theurl, M., Mair, S. M., Fritsche, G., et al. (2007). The co-ordinated regulation of iron homeostasis in murine macrophages limits the availability of iron for intracellular Salmonella typhimurium. Cell. Microbiol. 9, 2126-2140. doi: 10.1111/j.1462-5822.2007.00942.x
152. 2+ )-Fur is mediated by reversal of H-NS silencing and is RyhB independent. Mol. Microbiol. 75, 637-657. doi: 10.1111/j.1365-2958.2009.06977.x
153. Natori, Y., Nanamiya, H., Akanuma, G., Kosono, S., Kudo, T., Ochi, K., et al. (2007). A fail-safe system for the ribosome under zinc-limiting conditions in Bacillus subtilis. Mol. Microbiol. 63, 294-307. doi: 10.1111/j.1365-2958.2006.05513.x
154. Neilands, J. B. (1993). Siderophores. Arch. Biochem. Biophys. 302, 1-3. doi: 10.1006/abbi.1993.1172
155. Nemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., et al. (2004a). IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Invest. 113, 1271-1276.
156. Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., et al. (2004b). Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306, 2090-2093. doi: 10.1126/science.1104742
157. Nicolas, G., Chauvet, C., Viatte, L., Danan, J. L., Bigard, X., Devaux, I., et al. (2002). The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest. 110, 1037-1044.
158. Niederhoffer, E. C., Naranjo, C. M., Bradley, K. L., and Fee, J. A. (1990). Control of Escherichia coli superoxide dismutase (sodA and sodB) genes by the ferric uptake regulation (fur) locus. J. Bacteriol. 172, 1930-1938.
159. Oglesby, A. G., Murphy, E. R., Iyer, V. R., and Payne, S. M. (2005). Fur regulates acid resistance in Shigella flexneri via RyhB and ydeP. Mol. Microbiol. 58, 1354-1367. doi: 10.1111/j.1365-2958.2005.04920.x
160. Ogunniyi, A. D., Mahdi, L. K., Jennings, M. P., McEwan, A. G., McDevitt, C. A., Van Der Hoek, M. B., et al. (2010). Central role of manganese in regulation of stress responses, physiology, and metabolism in Streptococcus pneumoniae. J. Bacteriol. 192, 4489-4497. doi: 10.1128/JB.00064-10
161. Olekhnovich, I. N., and Kadner, R. J. (2006). Crucial roles of both flanking sequences in silencing of the hilA promoter in Salmonella enterica. J. Mol. Biol. 357, 373-386. doi: 10.1016/j.jmb.2006.01.007
162. Osorio, C. R., Lemos, M. L., and Braun, V. (2004). Identification of Fur regulated genes in the bacterial fish pathogen Photobacterium damselae ssp. piscicida using the Fur titration assay. Biometals 17, 725-733. doi: 10.1007/s10534-004-1652-7
163. Ouyang, Z., He, M., Oman, T., Yang, X. F., and Norgard, M. V. (2009). A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi. Proc. Natl. Acad. Sci. U.S.A. 106, 3449-3454. doi: 10.1073/pnas.0812999106
164. Palyada, K., Threadgill, D., and Stintzi, A. (2004). Iron acquisition and regulation in Campylobacter jejuni. J. Bacteriol. 186, 4714-4729. doi: 10.1128/JB.186.14.4714-4729.2004
165. Paradkar, P. N., De Domenico, I., Durchfort, N., Zohn, I., Kaplan, J., and Ward, D. M. (2008). Iron depletion limits intracellular bacterial growth in macrophages. Blood 112, 866-874. doi: 10.1182/blood-2007-12-126854
166. Patzer, S. I., and Hantke, K. (1998). The ZnuABC high-affinity zinc uptake system and its regulator Zur in Escherichia coli. Mol. Microbiol. 28, 1199-1210. doi: 10.1046/j.1365-2958.1998.00883.x
167. Patzer, S. I., and Hantke, K. (2000). The zinc-responsive regulator Zur and its control of the znu gene cluster encoding the ZnuABC zinc uptake system in Escherichia coli. J. Biol. Chem. 275, 24321-24332. doi: 10.1074/jbc.M001775200
168. 2+ ) transporter in Escherichia coli. J. Bacteriol. 183, 4806-4813. doi: 10.1128/JB.183.16.4806-4813.2001
169. Perry, R. D., Craig, S. K., Abney, J., Bobrov, A. G., Kirillina, O., Mier, I. Jr., et al. (2012). Manganese transporters Yfe and MntH are Fur-regulated and important for the virulence of Yersinia pestis. Microbiology 158, 804-815. doi: 10.1099/mic.0.053710-0
170. Pesciaroli, M., Aloisio, F., Ammendola, S., Pistoia, C., Petrucci, P., Tarantino, M., et al. (2011). An attenuated Salmonella enterica serovar Typhimurium strain lacking the ZnuABC transporter induces protection in a mouse intestinal model of Salmonella infection. Vaccine 29, 1783-1790. doi: 10.1016/j.vaccine.2010.12.111
171. Plant, J., and Glynn, A. A. (1976). Genetics of resistance to infection with Salmonella typhimurium in mice. J. Infect. Dis. 133, 72-78. doi: 10.1093/infdis/133.1.72
172. Prajapat, M. K., and Saini, S. (2012). Interplay between Fur and HNS in controlling virulence gene expression in Salmonella typhimurium. Comput. Biol. Med. 42, 1133-1140. doi: 10.1016/j.compbiomed.2012.09.005
173. Prentice, A. M., Doherty, C. P., Abrams, S. A., Cox, S. E., Atkinson, S. H., Verhoef, H., et al. (2012). Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children. Blood 119, 1922-1928. doi: 10.1182/blood-2011-11-391219
174. Rea, R., Hill, C., and Gahan, C. G. (2005). Listeria monocytogenes PerR mutants display a small-colony phenotype, increased sensitivity to hydrogen peroxide, and significantly reduced murine virulence. Appl. Environ. Microbiol. 71, 8314-8322. doi: 10.1128/AEM.71.12.8314-8322.2005
175. Rea, R. B., Gahan, C. G., and Hill, C. (2004). Disruption of putative regulatory loci in Listeria monocytogenes demonstrates a significant role for Fur and PerR in virulence. Infect. Immun. 72, 717-727. doi: 10.1128/IAI.72.2.717-727.2004
176. Richardson, A. R., Dunman, P. M., and Fang, F. C. (2006). The nitrosative stress response of Staphylococcus aureus is required for resistance to innate immunity. Mol. Microbiol. 61, 927-939. doi: 10.1111/j.1365-2958.2006.05290.x
177. Robbe-Saule, V., Coynault, C., Ibanez-Ruiz, M., Hermant, D., and Norel, F. (2001). Identification of a non-haem catalase in Salmonella and its regulation by RpoS (sigmaS). Mol. Microbiol. 39, 1533-1545. doi: 10.1046/j.1365-2958.2001.02340.x
178. Runyen-Janecky, L., Dazenski, E., Hawkins, S., and Warner, L. (2006). Role and regulation of the Shigella flexneri sit and MntH systems. Infect. Immun. 74, 4666-4672. doi: 10.1128/IAI.00562-06
179. Sabri, M., Houle, S., and Dozois, C. M. (2009). Roles of the extraintestinal pathogenic Escherichia coli ZnuACB and ZupT zinc transporters during urinary tract infection. Infect. Immun. 77, 1155-1164. doi: 10.1128/IAI.01082-08
180. Sadykov, M. R., Olson, M. E., Halouska, S., Zhu, Y., Fey, P. D., Powers, R., et al. (2008). Tricarboxylic acid cycle-dependent regulation of Staphylococcus epidermidis polysaccharide intercellular adhesin synthesis. J. Bacteriol. 190, 7621-7632. doi: 10.1128/JB.00806-08
181. Salvail, H., Lanthier-Bourbonnais, P., Sobota, J. M., Caza, M., Benjamin, J. A., Mendieta, M. E., et al. (2010). A small RNA promotes siderophore production through transcriptional and metabolic remodeling. Proc. Natl. Acad. Sci. U.S.A. 107, 15223-15228. doi: 10.1073/pnas.1007805107
182. Santander, J., Golden, G., Wanda, S. Y., and Curtiss, R. 3rd. (2012). Fur-regulated iron uptake system of Edwardsiella ictaluri and its influence on pathogenesis and immunogenicity in the catfish host. Infect. Immun. 80, 2689-2703. doi: 10.1128/IAI.00013-12
183. Schrum, L. W., and Hassan, H. M. (1994). The effects of fur on the transcriptional and post-transcriptional regulation of MnSOD gene (sodA) in Escherichia coli. Arch. Biochem. Biophys. 309, 288-292. doi: 10.1006/abbi.1994.1115
184. Shayeghi, M., Latunde-Dada, G. O., Oakhill, J. S., Laftah, A. H., Takeuchi, K., Halliday, N., et al. (2005). Identification of an intestinal heme transporter. Cell 122, 789-801. doi: 10.1016/j.cell.2005.06.025
185. Sheehan, B. J., Bosse, J. T., Beddek, A. J., Rycroft, A. N., Kroll, J. S., and Langford, P. R. (2003). Identification of Actinobacillus pleuropneumoniae genes important for survival during infection in its natural host. Infect. Immun. 71, 3960-3970. doi: 10.1128/IAI.71.7.3960-3970.2003
186. Skamene, E., Gros, P., Forget, A., Kongshavn, P. A., St Charles, C., and Taylor, B. A. (1982). Genetic regulation of resistance to intracellular pathogens. Nature 297, 506-509. doi: 10.1038/297506a0
187. Smith, K. D. (2007). Iron metabolism at the host pathogen interface: lipocalin 2 and the pathogen-associated iroA gene cluster. Int. J. Biochem. Cell Biol. 39, 1776-1780. doi: 10.1016/j.biocel.2007.07.003
188. Smith, K. F., Bibb, L. A., Schmitt, M. P., and Oram, D. M. (2009). Regulation and activity of a zinc uptake regulator, Zur, in Corynebacterium diphtheriae. J. Bacteriol. 191, 1595-1603. doi: 10.1128/JB.01392-08
189. Soler-Garcia, A. A., and Jerse, A. E. (2007). Neisseria gonorrhoeae catalase is not required for experimental genital tract infection despite the induction of a localized neutrophil response. Infect. Immun. 75, 2225-2233. doi: 10.1128/IAI.01513-06
190. Spears, P. A., Schauer, D., and Orndorff, P. E. (1986). Metastable regulation of type 1 piliation in Escherichia coli and isolation and characterization of a phenotypically stable mutant. J. Bacteriol. 168, 179-185.
191. Stojiljkovic, I., Baumler, A. J., and Hantke, K. (1994). Fur regulon in gram-negative bacteria. Identification and characterization of new iron-regulated Escherichia coli genes by a fur titration assay. J. Mol. Biol. 236, 531-545. doi: 10.1006/jmbi.1994.1163
192. Storz, G., Jacobson, F. S., Tartaglia, L. A., Morgan, R. W., Silveira, L. A., and Ames, B. N. (1989). An alkyl hydroperoxide reductase induced by oxidative stress in Salmonella typhimurium and Escherichia coli: genetic characterization and cloning of ahp. J. Bacteriol. 171, 2049-2055.
193. Tanabe, T., Funahashi, T., Moon, Y. H., Tamai, E., and Yamamoto, S. (2010). Identification and characterization of a Vibrio mimicus gene encoding the heme/hemoglobin receptor. Microbiol. Immunol. 54, 606-617.
194. Tardat, B., and Touati, D. (1991). Two global regulators repress the anaerobic expression of MnSOD in Escherichia coli::fur (ferric uptake regulation) and Arc (aerobic respiration control). Mol. Microbiol. 5, 455-465. doi: 10.1111/j.1365-2958.1991.tb02129.x
195. Tardat, B., and Touati, D. (1993). Iron and oxygen regulation of Escherichia coli MnSOD expression: competition between the global regulators Fur and ArcA for binding to DNA. Mol. Microbiol. 9, 53-63. doi: 10.1111/j.1365-2958.1993.tb01668.x
196. Tartaglia, L. A., Storz, G., and Ames, B. N. (1989). Identification and molecular analysis of oxyR-regulated promoters important for the bacterial adaptation to oxidative stress. J. Mol. Biol. 210, 709-719. doi: 10.1016/0022-2836(89)90104-6
197. Taylor, C. M., Osman, D., and Cavet, J. S. (2009). Differential expression from two iron-responsive promoters in Salmonella enterica serovar Typhimurium reveals the presence of iron in macrophage-phagosomes. Microb. Pathog. 46, 114-118. doi: 10.1016/j.micpath.2008.11.001
198. Tchawa Yimga, M., Leatham, M. P., Allen, J. H., Laux, D. C., Conway, T., and Cohen, P. S. (2006). Role of gluconeogenesis and the tricarboxylic acid cycle in the virulence of Salmonella enterica serovar Typhimurium in BALB/c mice. Infect. Immun. 74, 1130-1140. doi: 10.1128/IAI.74.2.1130-1140.2006
199. Teixido, L., Carrasco, B., Alonso, J. C., Barbe, J., and Campoy, S. (2011). Fur activates the expression of Salmonella enterica pathogenicity island 1 by directly interacting with the hilD operator in vivo and in vitro. PLoS ONE 6:e19711. doi: 10.1371/journal.pone.0019711
200. Thompson, A., Rolfe, M. D., Lucchini, S., Schwerk, P., Hinton, J. C., and Tedin, K. (2006). The bacterial signal molecule, ppGpp, mediates the environmental regulation of both the invasion and intracellular virulence gene programs of Salmonella. J. Biol. Chem. 281, 30112-30121. doi: 10.1074/jbc.M605616200
201. Torres, V. J., Attia, A. S., Mason, W. J., Hood, M. I., Corbin, B. D., Beasley, F. C., et al. (2010). Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia. Infect. Immun. 78, 1618-1628. doi: 10.1128/IAI.01423-09
202. Troxell, B., Fink, R. C., Porwollik, S., McClelland, M., and Hassan, H. M. (2011a). The Fur regulon in anaerobically grown Salmonella enterica sv. Typhimurium: identification of new Fur targets. BMC Microbiol. 11:236. doi: 10.1186/1471-2180-11-236
203. Troxell, B., Sikes, M. L., Fink, R. C., Vazquez-Torres, A., Jones-Carson, J., and Hassan, H. M. (2011b). Fur negatively regulates hns and is required for the expression of HilA and virulence in Salmonella enterica serovar Typhimurium. J. Bacteriol. 193, 497-505. doi: 10.1128/JB.00942-10
204. Troxell, B., Ye, M., Yang, Y., Carrasco, S. E., Lou, Y., and Yang, X. F. (2013). Manganese and zinc regulate virulence determinants in Borrelia burgdorferi. Infect. Immun. 81, 2743-2752. doi: 10.1128/IAI.00507-13
205. Tsolis, R. M., Baumler, A. J., Stojiljkovic, I., and Heffron, F. (1995). Fur regulon of Salmonella typhimurium: identification of new iron-regulated genes. J. Bacteriol. 177, 4628-4637.
206. Urban, J. H., and Vogel, J. (2007). Translational control and target recognition by Escherichia coli small RNAs in vivo. Nucleic Acids Res. 35, 1018-1037. doi: 10.1093/nar/gkl1040
207. Van Vliet, A. H., Baillon, M. L., Penn, C. W., and Ketley, J. M. (1999). Campylobacter jejuni contains two fur homologs: characterization of iron-responsive regulation of peroxide stress defense genes by the PerR repressor. J. Bacteriol. 181, 6371-6376.
208. Varghese, S., Wu, A., Park, S., Imlay, K. R., and Imlay, J. A. (2007). Submicromolar hydrogen peroxide disrupts the ability of Fur protein to control free-iron levels in Escherichia coli. Mol. Microbiol. 64, 822-830. doi: 10.1111/j.1365-2958.2007.05701.x
209. Vassinova, N., and Kozyrev, D. (2000). A method for direct cloning of fur-regulated genes: identification of seven new fur-regulated loci in Escherichia coli. Microbiology 146(Pt 12), 3171-3182.
210. Vazquez-Torres, A. (2012). Redox active thiol sensors of oxidative and nitrosative stress. Antioxid. Redox Signal. 17, 1201-1214. doi: 10.1089/ars.2012.4522
211. Velayudhan, J., Castor, M., Richardson, A., Main-Hester, K. L., and Fang, F. C. (2007). The role of ferritins in the physiology of Salmonella enterica sv. Typhimurium: a unique role for ferritin B in iron-sulphur cluster repair and virulence. Mol. Microbiol. 63, 1495-1507. doi: 10.1111/j.1365-2958.2007.05600.x
212. Veyrier, F. J., Boneca, I. G., Cellier, M. F., and Taha, M. K. (2011). A novel metal transporter mediating manganese export (MntX) regulates the Mn to Fe intracellular ratio and Neisseria meningitidis virulence. PLoS Pathog. 7:e1002261. doi: 10.1371/journal.ppat.1002261
213. Wang, H. R., Hu, Y. H., Zhang, W. W., and Sun, L. (2009). Construction of an attenuated Pseudomonas fluorescens strain and evaluation of its potential as a cross-protective vaccine. Vaccine 27, 4047-4055. doi: 10.1016/j.vaccine.2009.04.023
214. Weerakoon, D. R., Borden, N. J., Goodson, C. M., Grimes, J., and Olson, J. W. (2009). The role of respiratory donor enzymes in Campylobacter jejuni host colonization and physiology. Microb. Pathog. 47, 8-15. doi: 10.1016/j.micpath.2009.04.009
215. Weinberg, E. D. (1974). Iron and susceptibility to infectious disease. Science 184, 952-956. doi: 10.1126/science.184.4140.952
216. Weiss, G., Werner-Felmayer, G., Werner, E. R., Grunewald, K., Wachter, H., and Hentze, M. W. (1994). Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J. Exp. Med. 180, 969-976. doi: 10.1084/jem.180.3.969
217. Wilderman, P. J., Sowa, N. A., Fitzgerald, D. J., Fitzgerald, P. C., Gottesman, S., Ochsner, U. A., et al. (2004). Identification of tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa involved in iron homeostasis. Proc. Natl. Acad. Sci. U.S.A. 101, 9792-9797. doi: 10.1073/pnas.0403423101
218. Wintrobe, M. M., Greenberg, G. R., Humphreys, S. R., Ashen-Brucker, H., Worth, W., and Kramer, R. (1947). The Anemia of Infection. Iii. The uptake of radio-active iron in iron-deficient and in pyridoxine-deficient pigs before and after acute inflammation. J. Clin. Invest. 26, 103-113. doi: 10.1172/JCI101781
219. Wu, H. J., Seib, K. L., Srikhanta, Y. N., Edwards, J., Kidd, S. P., Maguire, T. L., et al. (2010). Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae. J. Proteomics 73, 899-916. doi: 10.1016/j.jprot.2009.12.001
220. Xiong, L., Ling, J., Gao, Q., Zhou, Y., Li, T., Gao, S., et al. (2012). Construction of iucB and iucBiutA mutants of avian pathogenic Escherichia coli and evaluation of their pathogenicity. Vet. Microbiol. 159, 420-431. doi: 10.1016/j.vetmic.2012.04.024
221. Yost, F. J. Jr., and Fridovich, I. (1973). An iron-containing superoxide dismutase from Escherichia coli. J. Biol. Chem. 248, 4905-4908.
222. Zheng, M., Doan, B., Schneider, T. D., and Storz, G. (1999). OxyR and SoxRS regulation of fur. J. Bacteriol. 181, 4639-4643.