Chapter 33 : Iron Metabolism, Transport, and Regulation

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This chapter discusses the wealth of knowledge about iron metabolism of by discussing mechanisms of iron transport, iron storage, and iron-responsive regulation of genes involved in iron metabolism. Most of the data discussed in the chapter have been obtained by using , but the author also discusses about the data obtained for ; it is thought that the mechanisms involved in iron metabolism are essentially similar in both species. The availability of free iron inside mammalian and avian hosts is extremely limited as a result of the toxicity of iron in combination with oxygen. Ferrous iron is utilized by many bacteria, and in , the high-affinity ferrous transport system expressed under anaerobic conditions involves two proteins, FeoA and FeoB, and a probable transcriptional regulator, FeoC. Enterobactin, which is produced by members of the mammalian and avian intestinal microbial flora, has the potential of being a significant source of iron to . Genes with homology to fhuABD, which encode the outer membrane receptor and part of the ABC transport system of the ferrichrome uptake system, have been identified in a set of strains. The other genes belonging to iron metabolism found to be upregulated in the rabbit intestine include those encoding Cj0236c, Cj0722c–Cj0723c, Cj1613c, PanBC, and RpmA. The transcriptomic analysis of genes involved in iron metabolism has highlighted some important connections between iron limitation and metabolism.

Citation: Stintzi A, van Vliet A, Ketley J. 2008. Iron Metabolism, Transport, and Regulation, p 591-610. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch33
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Image of Figure 1.
Figure 1.

Iron transport across the gram-negative cell envelope. (Left) TonB- and ABC-dependent transport pathway. Transport through the high-affinity outer membrane receptor is energized by TonB-mediated transduction of energy from the proton motive force with participation from ExbB and ExbD. Passage across the cytoplasmic membrane involves proteins of an ABC transporter system whose ATPase activity energizes the process. (Right) Ferrous iron uptake pathway. Ferrous iron crosses the outer membrane via a nonspecific porin or after reduction of ferric iron. The inner membrane FeoB containing a G protein domain and cytoplasmic FeoA transport the ferrous iron into the cytoplasm.

Citation: Stintzi A, van Vliet A, Ketley J. 2008. Iron Metabolism, Transport, and Regulation, p 591-610. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch33
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Image of Figure 2.
Figure 2.

Iron transport systems of as determined by comparative genome analysis and experimental data (see text for details). Substrates are shown where known, and systems present in all strains are highlighted.

Citation: Stintzi A, van Vliet A, Ketley J. 2008. Iron Metabolism, Transport, and Regulation, p 591-610. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch33
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Image of Figure 3.
Figure 3.

Overview of pathways involved in generation and inactivation of different forms of reactive oxygen species in , including superoxides (O ), hydrogen peroxide (HO), and alkyl peroxides (RHO).

Citation: Stintzi A, van Vliet A, Ketley J. 2008. Iron Metabolism, Transport, and Regulation, p 591-610. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch33
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Image of Figure 4.
Figure 4.

Roles of iron and Fur and PerR regulatory proteins in controlling iron metabolism and oxidative stress resistance in Arrows indicate connecting pathways.

Citation: Stintzi A, van Vliet A, Ketley J. 2008. Iron Metabolism, Transport, and Regulation, p 591-610. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch33
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1. Abdallah, F. B., and, J.-M. El Hage Chahine. 2000. Transferrins: iron release from lactoferrin. J. Mol. Biol. 303: 255266.
2. Adhikari, P.,, S. A. Berish,, A. J. Nowalk,, K. L. Veraldi,, S. A. Morde, and, T. A. Mietzer. 1996. The fbpABC locus of Neisseria gonorrhoeae functions in the periplasm-to-cytosol transport of iron. J. Bacteriol. 178: 21452149.
3. Almiron, M.,, A. J. Link,, D. Furlong, and, R. Kolter. 1992. A novel DNA-binding protein with regulatory and protective roles in starved Escherichia coli. Genes Dev. 6: 26462654.
4. Anderson, B. F.,, H. M. Baker,, E. J. Dodson,, G. E. Norris,, S. V. Rumball,, J. M. Waters, and, E. N. Baker. 1987. Structure of human lactoferrin at 3.2-Å resolution. Proc. Natl. Acad. Sci. USA 84: 17691773.
5. Anderson, J. E.,, P. F. Sparling, and, C. N. Cornelissen. 1994. Gonococcal transferrin-binding protein 2 facilitates but is not essential for transferrin utilization. J. Bacteriol. 176: 31623170.
6. Andrews, S. C. 1998. Iron storage in bacteria. Adv. Microb. Physiol. 40: 281351.
7. Andrews, S. C.,, A. K. Robinson, and, F. Rodriguez-Quinones. 2003. Bacterial iron homeostasis. FEMS Microbiol. Rev. 27: 215237.
8. Asakura, H.,, M. Yamasaki,, S. Yamamoto, and, S. Igimi. 2007. Deletion of peb4 gene impairs cell adhesion and biofilm formation in Campylobacter jejuni. FEMS Microbiol. Lett. 275: 278285.
9. Baig, B. H.,, I. K. Wachsmuth, and, G. K. Morris. 1986. Utilization of exogenous siderophores by Campylobacter species. J. Clin. Microbiol. 23: 431433.
10. Baillon, M. L. A.,, A. H. M. van Vliet,, J. M. Ketley,, C. Constantinidou, and, C. W. Penn. 1999. An iron-regulated alkyl hydro-peroxide reductase (AhpC) confers aerotolerance and oxidative stress resistance to the microaerophilic pathogen Campylobacter jejuni. J. Bacteriol. 181: 47984804.
11. Bereswill, S.,, U. Waidner,, S. Odenbreit,, F. Lichte,, F. Fassbinder,, G. Bode, and, M. Kist. 1998. Structural, functional and mutational analysis of the pfr gene encoding a ferritin from Helicobacter pylori. Microbiology 144: 25052516.
12. Bigas, A.,, M. A. Garrido,, I. Badiola,, J. Barbe, and, M. Llagostera. 2006. Non-viability of Haemophilus parasuis fur-defective mutants. Vet. Microbiol. 118: 107116.
13. Bijlsma, J. J. E.,, B. Waidner,, A. H. M. van Vliet,, N. J. Hughes,, S. Hag,, S. Bereswill,, D. J. Kelly,, C. M. J. E. Vandenbroucke-Grauls,, M. Kist, and, J. G. Kusters. 2002. The ferric uptake regulator (Fur) homologue of Helicobacter pylori is involved in acid resistance. Infect. Immun. 70: 606611.
14. Biswas, G. D., and, P. F. Sparling. 1995. Characterization of lbpA, the structural gene for a lactoferrin receptor in Neisseria gonorrhoeae. Infect. Immun. 63: 29582967.
15. Black, R. E.,, M. M. Levine,, M. L. Clements,, T. P. Hughes, and, M. J. Blaser. 1988. Experimental Campylobacter jejuni infection in humans. J. Infect. Dis. 157: 472479.
16. Bourke, B.,, S. T. al Rashid,, H. L. Bingham, and, V. L. Chan. 1996. Characterization of Campylobacter upsaliensis fur and its localization in a highly conserved region of the Campylobacter genome. Gene 183: 219224.
17. Braun, V., and, M. Braun. 2002. Active transport of iron and siderophore antibiotics. Curr. Opin. Microbiol. 5: 194201.
18. Braun, V.,, K. Hantke, and, W. Koster. 1998. Bacterial iron transport: mechanisms, genetics, and regulation. Met. Ions Biol. Syst. 35: 67145.
19. Bsat, N.,, A. Herbig,, L. Casillas-Martinez,, P. Setlow, and, J. D. Helmann. 1998. Bacillus subtilis contains multiple Fur homologues: identification of the iron uptake (Fur) and peroxide regulon (PerR) repressors. Mol. Microbiol. 29: 189198.
20. Carniel, E. 2001. The Yersinia high-pathogenicity island: an iron-uptake island. Microbes Infect. 3: 561569.
21. Cartron, M.,, S. Maddocks,, P. Gillingham,, C. Craven, and, S. Andrews. 2006. Feo-transport of ferrous iron into bacteria. Bio-metals 19: 143157.
22. Cawthraw, S.,, S. F. Park,, J. M. Ketley,, R. Ayling, and, D. G. Newell. 1996. The chick colonization model and its role in molecular biology studies of campylobacters, p. 649652. In D. G. Newell,, J. M. Ketley and, R. A. Feldman (ed.), Campylobacter, Helicobacter and Related Organisms, Plenum Press, New York.
23. Chan, A. C. K.,, B. Lelj-Garolla,, F. I. Rosell,, K. A. Pedersen,, A. G. Mauk, and, M. E. P. Murphy. 2006. Cofacial heme binding is linked to dimerization by a bacterial heme transport protein. J. Mol. Biol. 362: 11081119.
24. Chan, V. L.,, H. Louie, and, H. L. Bingham. 1995. Cloning and transcription regulation of the ferric uptake regulatory gene of Campylobacter jejuni TGH9011. Gene 164: 2531.
25. Chaudhuri, R. R., and, M. J. Pallen. 2006. xBASE, a collection of online databases for bacterial comparative genomics. Nucleic Acids Res. 34 (Database Issue): D335337.
26. Chelikani, P.,, I. Fita, and, P. C. Loewen. 2004. Diversity of structures and properties among catalases. Cell. Mol. Life. Sci. 61: 192208.
27. Chen, C.-Y.,, S. A. Berish,, S. A. Morse, and, T. A. Mietzner. 1993. The ferric iron-binding protein of pathogenic Neisseria spp. functions as a periplasmic transport protein in iron acquisition from human transferrin. Mol. Microbiol. 10: 311318.
28. Cogan, T. A.,, A. O. Thomas,, L. E. Rees,, A. H. Taylor,, M. A. Jepson,, P. H. Williams,, J. Ketley, and, T. J. Humphrey. 2007. Norepinephrine increases the pathogenic potential of Campylobacter jejuni. Gut 56: 10601065.
29. Conrad, M. E., and, S. G. Schade. 1968. Ascorbic acid chelates in iron absorption: a role for hydrochloric acid and bile. Gastroenterology 55: 3545.
30. Cooksley, C.,, P. J. Jenks,, A. Green,, A. Cockayne,, R. P. Logan, and, K. R. Hardie. 2003. NapA protects Helicobacter pylori from oxidative stress damage, and its production is influenced by the ferric uptake regulator. J. Med. Microbiol. 52: 461469.
31. Cope, L. D.,, S. E. Thomas,, Z. Hrkal, and, E. J. Hansen. 1998. Binding of heme-hemopexin complexes by soluble HxuA protein allows utilization of this complexed heme by Haemophilus influenzae. Infect. Immun. 66: 45114516.
32. Cope, L. D.,, R. Yogev,, U. Muller-Eberhard, and, E. J. Hansen. 1995. A gene cluster involved in the utilization of both free heme and heme:hemopexin by Haemophilus influenzae type b. J. Bacteriol. 177: 26442653.
33. Cornelissen, C. N.,, G. D. Biswas,, J. Tsai,, D. K. Paruchuri,, S. A. Thompson, and, P. F. Sparling. 1992. Gonococcal transferrin-binding protein 1 is required for transferrin utilization and is homologous to TonB-dependent outer membrane receptors. J. Bacteriol. 174: 57885797.
34. Day, W. A.,, J. L. Sajecki,, T. M. Pitts, and, L. A. Joens. 2000. Role of catalase in Campylobacter jejuni intracellular survival. Infect. Immun. 68: 63376345.
35. Deng, K.,, R. J. Blick,, W. Liu, and, E. J. Hansen. 2006. Identification of Francisella tularensis genes affected by iron limitation. Infect. Immun. 74: 42244236.
36. Dhaenens, L.,, F. Szczebara, and, M. O. Husson. 1997. Identification, characterization, and immunogenicity of the lactoferrin-binding protein from Helicobacter pylori. Infect. Immun. 65: 514518.
37. Dhaenens, L.,, F. Szczebara,, S. Van Nieuwenhuyse, and, M. O. Husson. 1999. Comparison of iron uptake in different Helicobacter species. Res. Microbiol. 150: 475481.
38. Dorrell, N.,, M. C. Martino,, R. A. Stabler,, S. J. Ward,, Z. W. Zhang,, A. A. McColm,, M. J. Farthing, and, B. W. Wren. 1999. Characterization of Helicobacter pylori PldA, a phospholipase with a role in colonization of the gastric mucosa. Gastroenterology 117: 10981104.
39. Dubbels, B. L.,, A. A. DiSpirito,, J. D. Morton,, J. D. Semrau,, J. N. Neto, and, D. A. Bazylinski. 2004. Evidence for a copper-dependent iron transport system in the marine, magnetotactic bacterium strain MV-1. Microbiology 150: 29312945.
40. Ducey, T. F.,, M. B. Carson,, J. Orvis,, A. P. Stintzi, and, D. W. Dyer. 2005. Identification of the iron-responsive genes of Neisseria gonorrhoeae by microarray analysis in defined medium. J. Bacteriol. 187: 48654874.
41. Ekins, A., and, D. F. Niven. 2002. Identification of fur and fldA homologs and a Pasteurella multocida tbpA homolog in Histophilus ovis and effects of iron availability on their transcription. J. Bacteriol. 184: 25392542.
42. Elvers, K. T.,, S. M. Turner,, L. M. Wainwright,, G. Marsden,, J. Hinds,, J. A. Cole,, R. K. Poole,, C. W. Penn, and, S. F. Park. 2005. NssR, a member of the Crp-Fnr superfamily from Campylobacter jejuni, regulates a nitrosative stress-responsive regulon that includes both a single-domain and a truncated haemoglobin. Mol. Microbiol. 57: 735750.
43. Escolar, L.,, J. Perez-Martin, and, V. de Lorenzo. 1999. Opening the iron-box: transcriptional metalloregulation by the Fur protein. J. Bacteriol. 181: 62236229.
44. Field, L. H.,, V. L. Headley,, S. M. Payne, and, L. J. Berry. 1986. Influence of iron on growth, morphology, outer membrane protein composition, and synthesis of siderophores in Campylobacter jejuni. Infect. Immun. 54: 126132.
45. Fox, E. M.,, M. Raftery,, A. Goodchild, and, G. L. Mendz. 2007. Campylobacter jejuni response to ox-bile stress. FEMS Immunol. Med. Microbiol. 49: 165172.
46. Freestone, P. P.,, R. D. Haigh,, P. H. Williams, and, M. Lyte. 2003. Involvement of enterobactin in norepinephrine-mediated iron supply from transferrin to enterohaemorrhagic Escherichia coli. FEMS Microbiol. Lett. 222: 3943.
47. Fuangthong, M.,, A. F. Herbig,, N. Bsat, and, J. D. Helmann. 2002. Regulation of the Bacillus subtilis fur and perR genes by PerR: not all members of the PerR regulon are peroxide inducible. J. Bacteriol. 184: 32763286.
48. Galindo, M. A.,, W. A. Day,, B. H. Raphael, and, L. A. Joens. 2001. Cloning and characterization of a Campylobacter jejuni iron-uptake operon. Curr. Microbiol. 42: 139143.
49. Genco, C. A., and, D. W. Dixon. 2001. Emerging strategies in microbial haem capture. Mol. Microbiol. 39: 111.
50. Ghigo, J. M.,, S. Letoffe, and, C. Wandersman. 1997. A new type of hemophore-dependent heme acquisition system of Serratia marcescens reconstituted in Escherichia coli. J. Bacteriol. 179: 35723579.
51. Giansanti, F.,, Rossi, P.,, Massucci, M. T.,, Botti, D.,, Antonini, G.,, Valenti, P., and, Seganti, L. 2002. Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin. Biochem. Cell Biol. 80: 125130.
52. Gomez, J. A.,, M. T. Criado, and, C. M. Ferreiros. 1998. Cooperation between the components of the meningococcal transferrin receptor, TbpA and TbpB, in the uptake of transferrin iron by the 37-kDa ferric-binding protein (FbpA). Res. Microbiol. 149: 381387.
53. Gorringe, A. R.,, G. Woods, and, A. Robinson. 1990. Growth and siderophore production by Bordetella pertussis under iron-restricted conditions. FEMS Microbiol. Lett. 54: 101105.
54. Grant, K. A.,, I. U. Belandia,, N. Dekker,, P. T. Richardson, and, S. F. Park. 1997. Molecular characterization of pldA, the structural gene for a phospholipase A from Campylobacter coli, and its contribution to cell-associated hemolysis. Infect. Immun. 65: 11721180.
55. Grant, K. A., and, S. F. Park. 1995. Molecular characterization of katA from Campylobacter jejuni and generation of a catalase-deficient mutant of Campylobacter coli by interspecific allelic exchange. Microbiology 141: 13691376.
56. Gray-Owen, S. D., and, A. B. Schryvers. 1996. Bacterial transferrin and lactoferrin receptors. Trends Microbiol. 4: 185191.
57. Grifantini, R.,, S. Sebastian,, E. Frigimelica,, M. Draghi,, E. Bartolini,, A. Muzzi,, R. Rappuoli,, G. Grandi, and, C. A. Genco. 2003. Identification of iron-activated and -repressed Fur-dependent genes by transcriptome analysis of Neisseria meningitidis group B. Proc. Natl. Acad. Sci. USA 100: 95429547.
58. Guerry, P.,, J. Perez-Casal,, R. Yao,, A. McVeigh, and, T. J. Trust. 1997. A genetic locus involved in iron utilization unique to some Campylobacter strains. J. Bacteriol. 179: 39974002.
59. Hannavy, K.,, G. C. Barr,, C. J. Dorman,, J. Adamson,, L. R. Mazengera,, M. P. Gallagher,, J. S. Evans,, B. A. Levine,, I. P. Trayer, and, C. F. Higgins. 1990. TonB protein of Salmonella typhimurium. A model for signal transduction between membranes. J. Mol. Biol. 216: 897910.
60. Hantke, K. 1997. Ferrous iron uptake by a magnesium transport system is toxic for Escherichia coli and Salmonella typhimurium. J. Bacteriol. 179: 62016204.
61. Hantke, K. 2001. Iron and metal regulation in bacteria. Curr. Opin. Microbiol. 4: 172177.
62. Henderson, D., and, S. Payne. 1994. Characterization of the Vibrio cholerae outer membrane heme transport protein HutA: sequence of the gene, regulation of expression, and homology to the family of TonB-dependent proteins. J. Bacteriol. 176: 32693277.
63. Herbig, A. F., and, J. D. Helmann. 2001. Roles of metal ions and hydrogen peroxide in modulating the interaction of the Bacillus subtilis PerR peroxide regulon repressor with operator DNA. Mol. Microbiol. 41: 849859.
64. Herrington, D. A., and, P. F. Sparling. 1985. Haemophilus influenzae can use human transferrin as a sole source for required iron. Infect. Immun. 48: 248251.
65. Hofreuter, D.,, J. Tsai,, R. O. Watson,, V. Novik,, B. Altman,, M. Benitez,, C. Clark,, C. Perbost,, T. Jarvie,, L. Du, and, J. E. Galan. 2006. Unique features of a highly pathogenic Campylobacter jejuni strain. Infect. Immun. 74: 46944707.
66. Holmes, K.,, F. Mulholland,, B. M. Pearson,, C. Pin,, J. McNicholl-Kennedy,, J. M. Ketley, and, J. M. Wells. 2005. Campylobacter jejuni gene expression in response to iron limitation and the role of Fur. Microbiology 151: 243257.
67. Hornung, J. M.,, H. A. Jones, and, R. D. Perry. 1996. The hmu locus of Yersinia pestis is essential for utilization of free haemin and haem-protein complexes as iron sources. Mol. Microbiol. 20: 725739.
68. Hughes, R. 2004. Campylobacter jejuni in Guillain-Barré syndrome. Lancet Neurol. 3: 644.
69. Husson, M. O.,, D. Legrand,, G. Spik, and, H. Leclerc. 1993. Iron acquisition by Helicobacter pylori: importance of human lactoferrin. Infect. Immun. 61: 26942697.
70. Ishikawa, T.,, Y. Mizunoe,, S. Kawabata,, A. Takade,, M. Harada,, S. N. Wai, and, S. Yoshida. 2003. The iron-binding protein Dps confers hydrogen peroxide stress resistance to Campylobacter jejuni. J. Bacteriol. 185: 10101017.
71. Jakubovics, N. S., and, H. F. Jenkinson. 2001. Out of the iron age: new insights into the critical role of manganese homeostasis in bacteria. Microbiology 147: 17091718.
72. Janvier, B.,, C. Constantinidou,, P. Aucher,, Z. V. Marshall,, C. W. Penn, and, J. L. Fauchere. 1998. Characterization and gene sequencing of a 19-kDa periplasmic protein of Campylobacter jejuni/coli. Res. Microbiol. 149: 95107.
73. Kalmokoff, M.,, P. Lanthier,, T. L. Tremblay,, M. Foss,, P. C. Lau,, G. Sanders,, J. Austin,, J. Kelly, and, C. M. Szymanski. 2006. Proteomic analysis of Campylobacter jejuni 11168 biofilms reveals a role for the motility complex in biofilm formation. J. Bacteriol. 188: 43124320.
74. Kammler, M.,, C. Schon, and, K. Hantke. 1993. Characterization of the ferrous iron uptake system of Escherichia coli. J. Bacteriol. 175: 62126219.
75. Ketley, J. M. 1997. Pathogenesis of enteric infection by Campylobacter. Microbiology 143: 521.
76. Knight, S. A. B.,, G. Vilaire,, E. Lesuisse, and, A. Dancis. 2005. Iron acquisition from transferrin by Candida albicans depends on the reductive pathway. Infect. Immun. 73: 54825492.
77. Lee, J. W., and, J. D. Helmann. 2007. Functional specialization within the Fur family of metalloregulators. Biometals 20: 485499.
78. Lee, J. W., and, J. D. Helmann. 2006. The PerR transcription factor senses H 2O 2 by metal-catalysed histidine oxidation. Nature 440: 363367.
79. Letoffe, S.,, P. Delepelaire, and, C. Wandersman. 2004. Free and hemophore-bound heme acquisitions through the outer membrane receptor HasR have different requirements for the TonB-ExbB-ExbD complex. J. Bacteriol. 186: 40674074.
80. Lewis, L. A.,, M. H. Sung,, M. Gipson,, K. Hartman, and, D. W. Dyer. 1998. Transport of intact porphyrin by HpuAB, the hemoglobin-haptoglobin utilization system of Neisseria meningitidis. J. Bacteriol. 180: 60436047.
81. Linton, K. J., and, C. F. Higgins. 1998. The Escherichia coli ATP-binding cassette (ABC) proteins. Mol. Microbiol. 28: 513.
82. Liu, Y., and, P. R. Ortiz de Montellano. 2000. Reaction intermediates and single turnover rate constants for the oxidation of heme by human heme oxygenase-1. J. Biol. Chem. 275: 52975307.
83. Lynch, M., and, H. Kuramitsu. 2000. Expression and role of superoxide dismutases (SOD) in pathogenic bacteria. Microbes Infect. 2: 12451255.
84. Ma, L.,, W. Kaserer,, R. Annamalai,, D. C. Scott,, B. Jin,, X. Jiang,, Q. Xiao,, H. Maymani,, L. M. Massis,, L. C. Ferreira,, S. M. Newton, and, P. E. Klebba. 2007. Evidence of ball-and-chain transport of ferric enterobactin through FepA. J. Biol. Chem. 282: 397406.
85. Madsen, M. L.,, D. Nettleton,, E. L. Thacker, and, F. C. Minion. 2006. Transcriptional profiling of Mycoplasma hyopneumoniae during iron depletion using microarrays. Microbiology 152: 937944.
86. Meimberg, K.,, N. Fischer,, J. D. Rochaix, and, U. Muhlenhoff. 1999. Lys35 of PsaC is required for the efficient photoreduction of flavodoxin by photosystem I from Chlamydomonas reinhardtii. Eur. J. Biochem. 263: 137144.
87. Menozzi, F. D.,, C. Gantiez, and, C. Locht. 1991. Identification and purification of transferrin- and lactoferrin-binding proteins of Bordetella pertussis and Bordetella bronchiseptica. Infect. Immun. 59: 39823988.
88. Merrell, D. S.,, L. J. Thompson,, C. C. Kim,, H. Mitchell,, L. S. Tompkins,, A. Lee, and, S. Falkow. 2003. Growth phase-dependent response of Helicobacter pylori to iron starvation. Infect. Immun. 71: 65106525.
89. Miethke, M.,, H. Westers,, E. J. Blom,, O. P. Kuipers, and, M. A. Marahiel. 2006. Iron starvation triggers the stringent response and induces amino acid biosynthesis for bacillibactin production in Bacillus subtilis. J. Bacteriol. 188: 86558657.
90. Miller, C. E.,, J. D. Rock,, K. A. Ridley,, P. H. Williams, and, J. M. Ketley. 2008. Utilizaton of lactoferrin-bound and transferrin-bound iron by Campylobacter jejuni. J. Bacteriol. 190: 19001911.
91. Mills, M., and, S. Payne. 1997. Identification of shuA, the gene encoding the heme receptor of Shigella dysenteriae, and analysis of invasion and intracellular multiplication of a shuA mutant. Infect. Immun. 65: 53585363.
92. Naikare, H.,, K. Palyada,, R. Panciera,, D. Marlow, and, A. Stintzi. 2006. Major role for FeoB in Campylobacter jejuni ferrous iron acquisition, gut colonization, and intracellular survival. Infect. Immun. 74: 54335444.
93. Occhino, D. A.,, E. E. Wyckoff,, D. P. Henderson,, T. J. Wrona, and, S. M. Payne. 1998. Vibrio cholerae iron transport: haem transport genes are linked to one of two sets of tonB, exbB, exbD genes. Mol. Microbiol. 29: 14931507.
94. Ochsner, U. A.,, Z. Johnson, and, M. L. Vasil. 2000. Genetics and regulation of two distinct haem-uptake systems, phu and has, in Pseudomonas aeruginosa. Microbiology 146: 185198.
95. Palyada, K.,, D. Threadgill, and, A. Stintzi. 2004. Iron acquisition and regulation in Campylobacter jejuni. J. Bacteriol. 186: 47144729.
96. Park, R. Y.,, H. Y. Sun,, M. H. Choi,, Y. H. Bai, and, S. H. Shin. 2005. Staphylococcus aureus siderophore-mediated iron-acquisition system plays a dominant and essential role in the utilization of transferrin-bound iron. J. Microbiol. 43: 183190.
97. Park, S. F. 1999. The use of hipO, encoding benzoylglycine amidohydrolase (hippuricase), as a reporter of gene expression in Campylobacter coli. Lett. Appl. Microbiol. 28: 285290.
98. Park, S. F., and, P. T. Richardson. 1995. Molecular characterization of a Campylobacter jejuni lipoprotein with homology to periplasmic siderophore-binding proteins. J. Bacteriol. 177: 22592264.
99. Parkhill, J.,, B. W. Wren,, K. Mungall,, J. M. Ketley,, C. Churcher,, D. Basham,, T. Chillingworth,, R. M. Davies,, T. Feltwell,, S. Holroyd,, K. Jagels,, A. V. Karlyshev,, S. Moule,, M. J. Pallen,, C. W. Penn,, M. A. Quail,, M. A. Rajandream,, K. M. Rutherford,, A. H. M. van Vliet,, S. Whitehead, and, B. G. Barrell. 2000. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403: 665668.
100. Pearson, B. M.,, D. J. Gaskin,, R. P. Segers,, J. M. Wells,, P. J. Nuijten, and, A. H. van Vliet. 2007. The complete genome sequence of Campylobacter jejuni strain 81116 (NCTC11828). J. Bacteriol. 189: 84028403.
101. Pesci, E. C.,, D. L. Cottle, and, C. L. Pickett. 1994. Genetic, enzymatic, and pathogenic studies of the iron superoxide dismutase of Campylobacter jejuni. Infect. Immun. 62: 26872694.
102. Pettersson, A.,, T. Prinz,, A. Umar,, J. van der Biezen, and, J. Tommassen. 1998. Molecular characterization of LbpB, the second lactoferrin-binding protein of Neisseria meningitidis. Mol. Microbiol. 27: 599610.
103. Pfeiffer, J.,, J. Guhl,, B. Waidner,, M. Kist, and, S. Bereswill. 2002. Magnesium uptake by CorA is essential for viability of the gastric pathogen Helicobacter pylori. Infect. Immun. 70: 39303934.
104. Pickett, C. L.,, T. Auffenberg,, E. C. Pesci,, V. L. Sheen, and, S. S. Jusuf. 1992. Iron acquisition and hemolysin production by Campylobacter jejuni. Infect. Immun. 60: 38723877.
105. Pidcock, K. A.,, J. A. Wooten,, B. A. Daley, and, T. L. Stull. 1988. Iron acquisition by Haemophilus influenzae. Infect. Immun. 56: 721725.
106. Pittman, M. S.,, K. T. Elvers,, L. Lee,, M. A. Jones,, R. K. Poole,, S. F. Park, and, D. J. Kelly. 2007. Growth of Campylobacter jejuni on nitrate and nitrite: electron transport to NapA and NrfA via NrfH and distinct roles for NrfA and the globin Cgb in protection against nitrosative stress. Mol. Microbiol. 63: 575590.
107. Poole, L. B.,, C. M. Reynolds,, Z. A. Wood,, P. A. Karplus,, H. R. Ellis, and, M. Li Calzi. 2000a. AhpF and other NADH:peroxiredoxin oxidoreductases, homologues of low M r thioredoxin reductase. Eur. J. Biochem. 267: 61266133.
108. Poole, R. K., and, M. N. Hughes. 2000b. New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress. Mol. Microbiol. 36: 775783.
109. Postle, K., and, R. A. Larsen. 2007. TonB-dependent energy transduction between outer and cytoplasmic membranes. Biometals 20: 453465.
110. Purdy, D.,, S. Cawthraw,, J. H. Dickinson,, D. G. Newell, and, S. F. Park. 1999. Generation of a superoxide dismutase (SOD)-deficient mutant of Campylobacter coli: evidence for the significance of SOD in Campylobacter survival and colonization. Appl. Environ. Microbiol. 65: 25402546.
111. Purdy, D., and, S. F. Park. 1994. Cloning, nucleotide sequence and characterization of a gene encoding superoxide dismutase from Campylobacter jejuni and Campylobacter coli. Microbiology 140: 12031208.
112. Raphael, B. H., and, L. A. Joens. 2003. FeoB is not required for ferrous iron uptake in Campylobacter jejuni. Can. J. Microbiol. 49: 727731.
113. Redhead, K.,, T. Hill, and, H. Chart. 1987. Interaction of lactoferrin and transferrins with the outer membrane of Bordetella pertussis. J. Gen. Microbiol. 133: 891898.
114. Richardson, P. T., and, S. F. Park. 1995. Enterochelin acquisition in Campylobacter coli: characterization of components of a binding-protein-dependent transport system. Microbiology 141: 31813191.
115. Ridley, K. A.,, J. D. Rock,, Y. Li, and, J. M. Ketley. 2006. Heme utilization in Campylobacter jejuni. J. Bacteriol. 188: 78627875.
116. Roehrig, S. C.,, H. Q. Tran,, V. Spehr,, N. Gunkel,, P. M. Selzer, and, H. J. Ullrich. 2007. The response of Mannheimia haemolytica to iron limitation: implications for the acquisition of iron in the bovine lung. Vet. Microbiol. 121: 316329.
117. Sampathkumar, B.,, S. Napper,, C. D. Carrillo,, P. Willson,, E. Taboada,, J. H. Nash,, A. A. Potter,, L. A. Babiuk, and, B. J. Allan. 2006. Transcriptional and translational expression patterns associated with immobilized growth of Campylobacter jejuni. Microbiology 152: 567577.
118. Schaible, U. E., and, S. H. Kaufmann. 2004. Iron and microbial infection. Nat. Rev. Microbiol. 2: 946953.
119. Seliger, S. S.,, A. R. Mey,, A. M. Valle, and, S. M. Payne. 2001. The two TonB systems of Vibrio cholerae: redundant and specific functions. Mol. Microbiol. 39: 801812.
120. Singh, P. K.,, M. R. Parsek,, E. P. Greenberg, and, M. J. Welsh. 2002. A component of innate immunity prevents bacterial biofilm development. Nature 417: 552555.
121. Smith, R. L., and, M. E. Maguire. 1998. Microbial magnesium transport: unusual transporters searching for identity. Mol. Microbiol. 28: 217226.
122. Sriyosachati, S., and, C. D. Cox. 1986. Siderophore-mediated iron acquisition from transferrin by Pseudomonas aeruginosa. Infect. Immun. 52: 885891.
123. St Maurice, M.,, N. Cremades,, M. A. Croxen,, G. Sisson,, J. Sancho, and, P. S. Hoffman. 2007. Flavodoxin:quinone reductase (FqrB): a redox partner of pyruvate:ferredoxin oxidoreductase that reversibly couples pyruvate oxidation to NADPH production in Helicobacter pylori and Campylobacter jejuni. J. Bacteriol. 189: 47644773.
124. Stead, D., and, S. F. Park. 2000. Roles of Fe superoxide dismutase and catalase in resistance of Campylobacter coli to freeze-thaw stress. Appl. Environ. Microbiol. 66: 31103112.
125. Stintzi, A.,, D. Marlow,, K. Palyada,, H. Naikare,, R. Panciera,, L. Whitworth, and, C. Clarke. 2005. Use of genome-wide expression profiling and mutagenesis to study the intestinal lifestyle of Campylobacter jejuni. Infect. Immun. 73: 17971810.
126. Stojiljkovic, I.,, M. Cobeljic, and, K. Hantke. 1993. Escherichia coli K-12 ferrous iron uptake mutants are impaired in their ability to colonize the mouse intestine. FEMS Microbiol. Lett. 108: 111115.
127. Stojiljkovic, I.,, J. Larson,, V. Hwa,, S. Anic, and, M. So. 1996. HmbR outer membrane receptors of pathogenic Neisseria spp.: iron-regulated, hemoglobin-binding proteins with a high level of primary structure conservation. J. Bacteriol. 178: 46704678.
128. Storz, G., and, J. A. Imlay. 1999. Oxidative stress. Curr. Opin. Microbiol. 2: 188194.
129. Suits, M. D.,, G. P. Pal,, K. Nakatsu,, A. Matte,, M. Cygler, and, Z. Jia. 2005. Identification of an Escherichia coli O157:H7 heme oxygenase with tandem functional repeats. Proc. Natl. Acad. Sci. USA 102: 1695516960.
130. Tannas, T.,, N. Dekker,, G. Bukholm,, J. J. E. Bijlsma, and, B. J. Appelmelk. 2001. Phase variation in the Helicobacter pylori phospholipase A gene and its role in acid adaptation. Infect. Immun. 69: 73347340.
131. Tom-Yew, S. A.,, D. T. Cui,, E. G. Bekker, and, M. E. Murphy. 2005. Anion-independent iron coordination by the Campylobacter jejuni ferric binding protein. J. Biol. Chem. 280: 92839290.
132. Tonello, F.,, W. G. Dundon,, B. Satin,, M. Molinari,, G. Tognon,, G. Grandi,, G. Del Giudice,, R. Rappuoli, and, C. Montecucco. 1999. The Helicobacter pylori neutrophil-activating protein is an iron-binding protein with dodecameric structure. Mol. Microbiol. 34: 238246.
133. Torres, A. G., and, S. M. Payne. 1997. Haem iron-transport system in enterohaemorrhagic Escherichia coli O157:H7. Mol. Microbiol. 23: 825833.
134. Touati, D. 2000. Iron and oxidative stress in bacteria. Arch. Biochem. Biophys. 373: 1–6.
135. Tsolis, R. M.,, A. J. Baumler,, F. Heffron, and, I. Stojiljkovic. 1996. Contribution of TonB- and Feo-mediated iron uptake to growth of Salmonella typhimurium in the mouse. Infect. Immun. 64: 45494556.
136. Tuanyok, A.,, H. S. Kim,, W. C. Nierman,, Y. Yu,, J. Dunbar,, R. A. Moore,, P. Baker,, M. Tom,, J. M. Ling, and, D. E. Woods. 2005. Genome-wide expression analysis of iron regulation in Burkholderia pseudomallei and Burkholderia mallei using DNA microarrays. FEMS Microbiol. Lett. 252: 327335.
137. van Vliet, A. H.,, J. D. Rock,, L. N. Madeleine, and, J. M. Ketley. 2000. The iron-responsive regulator Fur of Campylobacter jejuni is expressed from two separate promoters. FEMS Microbiol. Lett. 188: 115118.
138. van Vliet, A. H.,, K. G. Wooldridge, and, J. M. Ketley. 1998. Iron-responsive gene regulation in a Campylobacter jejuni fur mutant. J. Bacteriol. 180: 52915298.
139. van Vliet, A. H. M.,, M. L. A. Baillon,, C. W. Penn, and, J. M. Ketley. 1999. Campylobacter jejuni contains two Fur homologs: characterization of iron-responsive regulation of peroxide stress defense genes by the PerR repressor. J. Bacteriol. 181: 63716376.
140. van Vliet, A. H. M.,, M. L. A. Baillon,, C. W. Penn, and, J. M. Ketley. 2001. The iron-induced ferredoxin FdxA of Campylobacter jejuni is involved in aerotolerance. FEMS Microbiol. Lett. 196: 189193.
141. van Vliet, A. H. M., and, J. M. Ketley. 2001. Pathogenesis of enteric Campylobacter infection. J. Appl. Microbiol. 90: 45S- 56S.
142. van Vliet, A. H. M.,, J. M. Ketley,, S. F. Park, and, C. W. Penn. 2002. The role of iron in Campylobacter gene regulation, metabolism and oxidative stress defense. FEMS Microbiol. Rev. 26: 173186.
143. Velayudhan, J.,, N. J. Hughes,, A. A. McColm,, J. Bagshaw,, C. L. Clayton,, S. C. Andrews, and, D. J. Kelly. 2000. Iron acquisition and virulence in Helicobacter pylori: a major role for FeoB, a high-affinity ferrous iron transporter. Mol. Microbiol. 37: 274286.
144. Wai, S. N.,, K. Nakayama,, K. Umene,, T. Moriya, and, K. Amako. 1996. Construction of a ferritin-deficient mutant of Campylobacter jejuni: contribution of ferritin to iron storage and protection against oxidative stress. Mol. Microbiol. 20: 11271134.
145. Wai, S. N.,, T. Takata,, A. Takade,, N. Hamasaki, and, K. Amako. 1995. Purification and characterization of ferritin from Campylobacter jejuni. Arch. Microbiol. 164: 16.
146. Waidner, B.,, S. Greiner,, S. Odenbreit,, H. Kavermann,, J. Velayudhan,, F. Stahler,, J. Guhl,, E. Bisse,, A. H. M. van Vliet,, S. C. Andrews,, J. G. Kusters,, D. J. Kelly,, R. Haas,, M. Kist, and, S. Bereswill. 2002. Essential role of ferritin Pfr in Helicobacter pylori iron metabolism and gastric colonization. Infect. Immun. 70: 39233929.
147. Wainwright, L. M.,, K. T. Elvers,, S. F. Park, and, R. K. Poole. 2005. A truncated haemoglobin implicated in oxygen metabolism by the microaerophilic food-borne pathogen Campylobacter jejuni. Microbiology 151: 40794091.
148. Wainwright, S. A.,, J. Velayudhan, and, D. J. Kelly. 2001. The magnesium transporter CorA catalyses low-affinity iron uptake in Helicobacter pylori. Int. J. Med. Microbiol. 291: 100.
149. Wang, G.,, P. Alamuri, and, R. J. Maier. 2006. The diverse anti-oxidant systems of Helicobacter pylori. Mol. Microbiol. 61: 847860.
150. Ward, P. P., and, O. M. Conneely. 2004. Lactoferrin: role in iron homeostasis and host defense against microbial infection. Biometals 17: 203208.
151. Whitby, P. W.,, T. M. Vanwagoner,, T. W. Seale,, D. J. Morton, and, T. L. Stull. 2006. Transcriptional profile of Haemophilus influenzae: effects of iron and heme. J. Bacteriol. 188: 56405645.
152. Woodall, C. A.,, M. A. Jones,, P. A. Barrow,, J. Hinds,, G. L. Mars-den,, D. J. Kelly,, N. Dorrell,, B. W. Wren, and, D. J. Maskell. 2005. Campylobacter jejuni gene expression in the chick cecum: evidence for adaptation to a low-oxygen environment. Infect. Immun. 73: 52785285.
153. Wooldridge, K. G., and, A. H. M. van Vliet. 2005. Iron transport and regulation, p. 293310. In J. M. Ketley and, M. Konkel (ed.), Campylobacter: Molecular and Cellular Biology. Horizon Scientific Press, Norfolk, United Kingdom.
154. Wooldridge, K. G., and, P. H. Williams. 1993. Iron uptake mechanisms of pathogenic bacteria. FEMS Microbiol. Rev. 12: 325348.
155. Wooldridge, K. G.,, P. H. Williams, and, J. M. Ketley. 1994. Iron-responsive genetic regulation in Campylobacter jejuni: cloning and characterization of a fur homolog. J. Bacteriol. 176: 58525856.
156. Wyckoff, E. E.,, M. Schmitt,, A. Wilks, and, S. M. Payne. 2004. HutZ is required for efficient heme utilization in Vibrio cholerae. J. Bacteriol. 186: 41424151.
157. Yamasaki, M.,, S. Igimi,, Y. Katayama,, S. Yamamoto, and, F. Amano. 2004. Identification of an oxidative stress-sensitive protein from Campylobacter jejuni, homologous to rubredoxin oxidoreductase/rubrerythrin. FEMS Microbiol. Lett. 235: 5763.
158. Yuki, N., and, M. Koga. 2006. Bacterial infections in Guillain-Barré and Fisher syndromes. Curr. Opin. Neurol. 19: 451457.
159. Zheng, M.,, B. Doan,, T. D. Schneider, and, G. Storz. 1999. OxyR and SoxRS regulation of fur. J. Bacteriol. 181: 46394643.
160. Zhou, D.,, L. Qin,, Y. Han,, J. Qiu,, Z. Chen,, B. Li,, Y. Song,, J. Wang,, Z. Guo,, J. Zhai,, Z. Du,, X. Wang, and, R. Yang. 2006. Global analysis of iron assimilation and fur regulation in Yersinia pestis. FEMS Microbiol. Lett. 258: 917.
161. Zhu, W.,, A. Wilks, and, I. Stojiljkovic. 2000. Degradation of heme in gram-negative bacteria: the product of the hemO gene of Neisseriae is a heme oxygenase. J. Bacteriol. 182: 67836790.


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Table 1.

genes differentially expressed between iron-rich and iron-restricted growth conditions

Citation: Stintzi A, van Vliet A, Ketley J. 2008. Iron Metabolism, Transport, and Regulation, p 591-610. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch33

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