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Metallobiology of Tuberculosis

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  • Authors: G. Marcela Rodriguez1, Olivier Neyrolles2
  • Editors: Graham F. Hatfull3, William R. Jacobs Jr.4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Public Health Research Institute and New Jersey Medical School-Rutgers, the State University of New Jersey, Newark, NJ 07103; 2: Centre National de la Recherche Scientifique and Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; 3: University of Pittsburgh, Pittsburgh, PA; 4: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY
  • Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0012-2013
  • Received 19 April 2013 Accepted 05 August 2013 Published 30 May 2014
  • O. Neyrolles, olivier.neyrolles@ipbs.fr
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  • Abstract:

    Transition metals are essential constituents of all living organisms, playing crucial structural and catalytic parts in many enzymes and transcription factors. However, transition metals can also be toxic when present in excess. Their uptake and efflux rates must therefore be carefully controlled by biological systems. In this chapter, we summarize the current knowledge about uptake and efflux systems in for mainly three of these metals, namely iron, zinc, and copper. We also propose questions for future research in the field of metallobiology of host-pathogen interactions in tuberculosis.

  • Citation: Marcela Rodriguez G, Neyrolles O. 2014. Metallobiology of Tuberculosis. Microbiol Spectrum 2(3):MGM2-0012-2013. doi:10.1128/microbiolspec.MGM2-0012-2013.

Key Concept Ranking

Resistance-Nodulation-Cell Division Superfamily
0.48658904
Outer Membrane Proteins
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0.48658904

References

1. Andrews SC, Robinson AK, Rodriguez-Quinones F. 2003. Bacterial iron homeostasis. FEMS Microbiol Rev 27:215–237. [PubMed][CrossRef]
2. Hood MI, Skaar EP. 2012. Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol 10:525–537. [PubMed][CrossRef]
3. Weinberg ED. 1974. Iron and susceptibility to infectious disease. Science 184:952–956. [PubMed][CrossRef]
4. Dobryszycka W. 1997. Biological functions of haptoglobin: new pieces to an old puzzle. Eur J Clin Chem Clin Biochem 35:647–654. [PubMed]
5. Tolosano E, Altruda F. 2002. Hemopexin: structure, function, and regulation. DNA Cell Biol 21:297–306. [PubMed][CrossRef]
6. Snow GA. 1970. Mycobactins: iron-chelating growth factors from mycobacteria. Bacteriol Rev 34:99–125. [PubMed]
7. Madigan CA, Cheng TY, Layre E, Young DC, McConnell MJ, Debono CA, Murry JP, Wei JR, Barry CE 3rd, Rodriguez GM, Matsunaga I, Rubin EJ, Moody DB. 2012. Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 109:1257–1262. [PubMed][CrossRef]
8. McMahon MD, Rush JS, Thomas MG. 2012. Analyses of MbtB, MbtE, and MbtF suggest revisions to the mycobactin biosynthesis pathway in Mycobacterium tuberculosis. J Bacteriol 194:2809–2818. [PubMed][CrossRef]
9. Quadri LE, Sello J, Keating TA, Weinreb PH, Walsh CT. 1998. Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chem Biol 5:631–645. [PubMed][CrossRef]
10. Gobin J, Moore CH, Reeve JR Jr, Wong DK, Gibson BW, Horwitz MA. 1995. Iron acquisition by Mycobacterium tuberculosis: isolation and characterization of a family of iron-binding exochelins. Proc Natl Acad Sci USA 92:5189–5193. [PubMed][CrossRef]
11. Ratledge C, Dover LG. 2000. Iron metabolism in pathogenic bacteria. Annu Rev Microbiol 54:881–941. [PubMed][CrossRef]
12. Gobin J, Horwitz MA. 1996. Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall. J Exp Med 183:1527–1532. [PubMed][CrossRef]
13. Rodriguez GM, Gardner R, Kaur N, Phanstiel O, 4th. 2008. Utilization of Fe3+-acinetoferrin analogs as an iron source by Mycobacterium tuberculosis. Biometals 21:93–103. [PubMed][CrossRef]
14. Wells RM, Jones CM, Xi Z, Speer A, Danilchanka O, Doornbos KS, Sun P, Wu F, Tian C, Niederweis M. 2013. Discovery of a siderophore export system essential for virulence of Mycobacterium tuberculosis. PLoS Pathogns 9:e1003120. [PubMed][CrossRef]
15. Rodriguez GM, Smith I. 2006. Identification of an ABC transporter required for iron acquisition and virulence in Mycobacterium tuberculosis. J Bacteriol 188:424–430. [PubMed][CrossRef]
16. Ryndak MB, Wang S, Smith I, Rodriguez GM. 2010. The Mycobacterium tuberculosis high-affinity iron importer, IrtA, contains an FAD-binding domain. J Bacteriol 192:861–869. [PubMed][CrossRef]
17. Serafini A, Boldrin F, Palu G, Manganelli R. 2009. Characterization of a Mycobacterium tuberculosis ESX-3 conditional mutant: essentiality and rescue by iron and zinc. J Bacteriol 191:6340–6344. [PubMed][CrossRef]
18. Siegrist MS, Unnikrishnan M, McConnell MJ, Borowsky M, Cheng TY, Siddiqi N, Fortune SM, Moody DB, Rubin EJ. 2009. Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proc Natl Acad Sci USA 106:18792–18797. [PubMed][CrossRef]
19. Jones CM, Niederweis M. 2011. Mycobacterium tuberculosis can utilize heme as an iron source. J Bacteriol 193:1767–1770. [PubMed][CrossRef]
20. Tullius MV, Harmston CA, Owens CP, Chim N, Morse RP, McMath LM, Iniguez A, Kimmey JM, Sawaya MR, Whitelegge JP, Horwitz MA, Goulding CW. 2011. Discovery and characterization of a unique mycobacterial heme acquisition system. Proc Natl Acad Sci USA 108:5051–5056. [PubMed][CrossRef]
21. Nambu S, Matsui T, Goulding CW, Takahashi S, Ikeda-Saito M. 2013. A new way to degrade heme: the Mycobacterium tuberculosis enzyme MhuD catalyzes heme degradation without generating CO. J Biol Chem 5:10101–10109. [PubMed][CrossRef]
22. Chiancone E, Ceci P, Ilari A, Ribacchi F, Stefanini S. 2004. Iron and proteins for iron storage and detoxification. Biometals 17:197–202. [PubMed][CrossRef]
23. Gupta V, Gupta RK, Khare G, Salunke DM, Tyagi AK. 2009. Crystal structure of Bfr A from Mycobacterium tuberculosis: incorporation of selenomethionine results in cleavage and demetallation of haem. PLoS One 4:e8028. [PubMed][CrossRef]
24. Khare G, Gupta V, Nangpal P, Gupta RK, Sauter NK, Tyagi AK. 2011. Ferritin structure from Mycobacterium tuberculosis: comparative study with homologues identifies extended C-terminus involved in ferroxidase activity. PLoS One 6:e18570. [PubMed][CrossRef]
25. Pandey R, Rodriguez GM. 2012. A ferritin mutant of Mycobacterium tuberculosis is highly susceptible to killing by antibiotics and is unable to establish a chronic infection in mice. Infect Immun 80:3650–3659. [PubMed][CrossRef]
26. Reddy PV, Puri RV, Khera A, Tyagi AK. 2012. Iron storage proteins are essential for the survival and pathogenesis of Mycobacterium tuberculosis in THP-1 macrophages and the guinea pig model of infection. J Bacteriol 194:567–575. [PubMed][CrossRef]
27. Takatsuka M, Osada-Oka M, Satoh EF, Kitadokoro K, Nishiuchi Y, Niki M, Inoue M, Iwai K, Arakawa T, Shimoji Y, Ogura H, Kobayashi K, Rambukkana A, Matsumoto S. 2011. A histone-like protein of mycobacteria possesses ferritin superfamily protein-like activity and protects against DNA damage by Fenton reaction. PLoS One 6:e20985. [PubMed][CrossRef]
28. Rodriguez GM, Voskuil MI, Gold B, Schoolnik GK, Smith I. 2002. ideR, An essential gene in Mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect Immun 70:3371–3381. [PubMed][CrossRef]
29. Schmitt MP, Predich M, Doukhan L, Smith I, Holmes RK. 1995. Characterization of an iron-dependent regulatory protein (IdeR) of Mycobacterium tuberculosis as a functional homolog of the diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae. Infect Immun 63:4284–4289. [PubMed]
30. Pohl E, Holmes RK, Hol WG. 1999. Crystal structure of the iron-dependent regulator (IdeR) from Mycobacterium tuberculosis shows both metal binding sites fully occupied. J Mol Biol 285:1145–1156. [PubMed][CrossRef]
31. Semavina M, Beckett D, Logan TM. 2006. Metal-linked dimerization in the iron-dependent regulator from Mycobacterium tuberculosis. Biochemistry 45:12480–12490. [PubMed][CrossRef]
32. Gold B, Rodriguez GM, Marras SA, Pentecost M, Smith I. 2001. The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol Microbiol 42:851–865. [PubMed][CrossRef]
33. Petrera A, Amstutz B, Gioia M, Hahnlein J, Baici A, Selchow P, Ferraris DM, Rizzi M, Sbardella D, Marini S, Coletta M, Sander P. 2012. Functional characterization of the Mycobacterium tuberculosis zinc metallopeptidase Zmp1 and identification of potential substrates. Biol Chem 393:631–640. [PubMed][CrossRef]
34. Srinivasan R, Anilkumar G, Rajeswari H, Ajitkumar P. 2006. Functional characterization of AAA family FtsH protease of Mycobacterium tuberculosis. FEMS Microbiol Lett 259:97–105. [PubMed][CrossRef]
35. Supuran CT. 2008. Carbonic anhydrases: an overview. Curr Pharm Des 14:603–614. [PubMed][CrossRef]
36. Pegan SD, Rukseree K, Franzblau SG, Mesecar AD. 2009. Structural basis for catalysis of a tetrameric class IIa fructose 1,6-bisphosphate aldolase from Mycobacterium tuberculosis. J Mol Biol 386:1038–1053. [PubMed][CrossRef]
37. Ordonez H, Unciuleac M, Shuman S. 2012. Mycobacterium smegmatis RqlH defines a novel clade of bacterial RecQ-like DNA helicases with ATP-dependent 3′-5′ translocase and duplex unwinding activities. Nucleic Acids Res 40:4604–4614. [PubMed][CrossRef]
38. Sanchez-Quitian ZA, Schneider CZ, Ducati RG, de Azevedo WF Jr, Bloch C Jr, Basso LA, Santos DS. 2010. Structural and functional analyses of Mycobacterium tuberculosis Rv3315c-encoded metal-dependent homotetrameric cytidine deaminase. J Struct Biol 169:413–423. [PubMed][CrossRef]
39. Tremblay LW, Fan F, Vetting MW, Blanchard JS. 2008. The 1.6 A crystal structure of Mycobacterium smegmatis MshC: the penultimate enzyme in the mycothiol biosynthetic pathway. Biochemistry 47:13326–13335. [PubMed][CrossRef]
40. Buetow L, Brown AC, Parish T, Hunter WN. 2007. The structure of mycobacteria 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery. BMC Struct Biol 7:68. [PubMed][CrossRef]
41. Koon N, Squire CJ, Baker EN. 2004. Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. Proc Natl Acad Sci USA 101:8295–8300. [PubMed][CrossRef]
42. Piddington DL, Fang FC, Laessig T, Cooper AM, Orme IM, Buchmeier NA. 2001. Cu,Zn superoxide dismutase of Mycobacterium tuberculosis contributes to survival in activated macrophages that are generating an oxidative burst. Infect Immun 69:4980–4987. [PubMed][CrossRef]
43. Wu CH, Tsai-Wu JJ, Huang YT, Lin CY, Lioua GG, Lee FJ. 1998. Identification and subcellular localization of a novel Cu,Zn superoxide dismutase of Mycobacterium tuberculosis. FEBS Lett 439:192–196. [PubMed][CrossRef]
44. Ilghari D, Lightbody KL, Veverka V, Waters LC, Muskett FW, Renshaw PS, Carr MD. 2011. Solution structure of the Mycobacterium tuberculosis EsxG.EsxH complex: functional implications and comparisons with other M. tuberculosis Esx family complexes. J Biol Chem 286:29993–30002. [PubMed][CrossRef]
45. Norman RA, McAlister MS, Murray-Rust J, Movahedzadeh F, Stoker NG, McDonald NQ. 2002. Crystal structure of inositol 1-phosphate synthase from Mycobacterium tuberculosis, a key enzyme in phosphatidylinositol synthesis. Structure 10:393–402. [PubMed][CrossRef]
46. Zhang L, Xiao N, Pan Y, Zheng Y, Pan Z, Luo Z, Xu X, Liu Y. 2010. Binding and inhibition of copper ions to RecA inteins from Mycobacterium tuberculosis. Chemistry 16:4297–4306. [PubMed][CrossRef]
47. Hantke K. 2005. Bacterial zinc uptake and regulators. Curr Opin Microbiol 8:196–202. [PubMed][CrossRef]
48. Nies DH. 2003. Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol Rev 27:313–339. [PubMed][CrossRef]
49. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544. [PubMed][CrossRef]
50. Verkhovtseva NV, Filina N, Pukhov DE. 2001. Evolutionary role of iron in metabolism of prokaryotes and biogeochemical processes. Zhurnal evoliutsionnoi biokhimii i fiziologii 37:338–343. (In Russian.) [PubMed]
51. Cavet JS, Meng W, Pennella MA, Appelhoff RJ, Giedroc DP, Robinson NJ. 2002. A nickel-cobalt-sensing ArsR-SmtB family repressor. Contributions of cytosol and effector binding sites to metal selectivity. J Biol Chem 277:38441–38448. [PubMed][CrossRef]
52. Botella H, Peyron P, Levillain F, Poincloux R, Poquet Y, Brandli I, Wang C, Tailleux L, Tilleul S, Charriere GM, Waddell SJ, Foti M, Lugo-Villarino G, Gao Q, Maridonneau-Parini I, Butcher PD, Castagnoli PR, Gicquel B, de Chastellier C, Neyrolles O. 2011. Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe 10:248–259. [PubMed][CrossRef]
53. Ward SK, Abomoelak B, Hoye EA, Steinberg H, Talaat AM. 2010. CtpV: a putative copper exporter required for full virulence of Mycobacterium tuberculosis. Mol Microbiol 77:1096–1110. [PubMed][CrossRef]
54. Fu Y, Tsui HC, Bruce KE, Sham LT, Higgins KA, Lisher JP, Kazmierczak KM, Maroney MJ, Dann CE 3rd, Winkler ME, Giedroc DP. 2013. A new structural paradigm in copper resistance in Streptococcus pneumoniae. Nat Chem Biol 9:177–183. [PubMed][CrossRef]
55. Festa RA, Jones MB, Butler-Wu S, Sinsimer D, Gerads R, Bishai WR, Peterson SN, Darwin KH. 2011. A novel copper-responsive regulon in Mycobacterium tuberculosis. Mol Microbiol 79:133–148. [PubMed][CrossRef]
56. Ward SK, Hoye EA, Talaat AM. 2008. The global responses of Mycobacterium tuberculosis to physiological levels of copper. J Bacteriol 190:2939–2946. [PubMed][CrossRef]
57. Liu T, Ramesh A, Ma Z, Ward SK, Zhang L, George GN, Talaat AM, Sacchettini JC, Giedroc DP. 2007. CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator. Nat Chem Biol 3:60–68. [PubMed][CrossRef]
58. Wolschendorf F, Ackart D, Shrestha TB, Hascall-Dove L, Nolan S, Lamichhane G, Wang Y, Bossmann SH, Basaraba RJ, Niederweis M. 2011. Copper resistance is essential for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci USA 108:1621–1626. [PubMed][CrossRef]
59. Botella H, Stadthagen G, Lugo-Villarino G, de Chastellier C, Neyrolles O. 2012. Metallobiology of host-pathogen interactions: an intoxicating new insight. Trends Microbiol 20:106–112. [PubMed][CrossRef]
60. Rowland JL, Niederweis M. 2012. Resistance mechanisms of Mycobacterium tuberculosis against phagosomal copper overload. Tuberculosis (Edinb) 92:202–210. [PubMed][CrossRef]
61. Samanovic MI, Ding C, Thiele DJ, Darwin KH. 2012. Copper in microbial pathogenesis: meddling with the metal. Cell Host Microbe 11:106–115. [PubMed][CrossRef]
62. White C, Lee J, Kambe T, Fritsche K, Petris MJ. 2009. A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem 284:33949–33956. [PubMed][CrossRef]
63. Padilla-Benavides T, Long JE, Raimunda D, Sassetti CM, Arguello JM. 2013. A novel P1B-type Mn2+ transporting ATPase is required for secreted protein metallation in mycobacteria. J Biol Chem 288:11334–11347. [PubMed][CrossRef]
64. Francis MS, Thomas CJ. 1997. Mutants in the CtpA copper transporting P-type ATPase reduce virulence of Listeria monocytogenes. Microbial Pathog 22:67–78. [PubMed][CrossRef]
65. Schwan WR, Warrener P, Keunz E, Stover CK, Folger KR. 2005. Mutations in the cueA gene encoding a copper homeostasis P-type ATPase reduce the pathogenicity of Pseudomonas aeruginosa in mice. Int J Med Microbiol 295:237–242. [PubMed][CrossRef]
66. Shafeeq S, Yesilkaya H, Kloosterman TG, Narayanan G, Wandel M, Andrew PW, Kuipers OP, Morrissey JA. 2011. The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae. Mol Microbiol 81:1255–1270. [PubMed][CrossRef]
67. Osman D, Waldron KJ, Denton H, Taylor CM, Grant AJ, Mastroeni P, Robinson NJ, Cavet JS. 2010. Copper homeostasis in salmonella is atypical and copper-CueP is a major periplasmic metal complex. J Biol Chem 285:25259–25268. [PubMed][CrossRef]
68. Macomber L, Rensing C, Imlay JA. 2007. Intracellular copper does not catalyze the formation of oxidative DNA damage in Escherichia coli. J Bacteriol 189:1616–1626. [PubMed][CrossRef]
69. Chillappagari S, Seubert A, Trip H, Kuipers OP, Marahiel MA, Miethke M. 2010. Copper stress affects iron homeostasis by destabilizing iron-sulfur cluster formation in Bacillus subtilis. J Bacteriol 192:2512–2524. [PubMed][CrossRef]
70. Xu FF, Imlay JA. 2012. Silver(I), mercury(II), cadmium(II), and zinc(II) target exposed enzymic iron-sulfur clusters when they toxify Escherichia coli. Appl Environ Microbiol 78:3614–3621. [PubMed][CrossRef]
71. McDevitt CA, Ogunniyi AD, Valkov E, Lawrence MC, Kobe B, McEwan AG, Paton JC. 2011. A molecular mechanism for bacterial susceptibility to zinc. PLoS Pathog 7:e1002357. [PubMed][CrossRef]
72. Osman D, Patterson CJ, Bailey K, Fisher K, Robinson NJ, Rigby SE, Cavet JS. 2013. The copper supply pathway to a salmonella Cu,Zn-superoxide dismutase (SodCII) involves P(1B)-type ATPase copper efflux and periplasmic CueP. Mol Microbiol 87:466–477. [PubMed][CrossRef]
73. Lucarelli D, Russo S, Garman E, Milano A, Meyer-Klaucke W, Pohl E. 2007. Crystal structure and function of the zinc uptake regulator FurB from Mycobacterium tuberculosis. J Biol Chem 282:9914–9922. [PubMed][CrossRef]
74. Maciag A, Dainese E, Rodriguez GM, Milano A, Provvedi R, Pasca MR, Smith I, Palu G, Riccardi G, Manganelli R. 2007. Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon. J Bacteriol 189:730–740. [PubMed][CrossRef]
75. Milano A, Branzoni M, Canneva F, Profumo A, Riccardi G. 2004. The Mycobacterium tuberculosis Rv2358-furB operon is induced by zinc. Res Microbiol 155:192–200. [PubMed][CrossRef]
76. Pym AS, Domenech P, Honore N, Song J, Deretic V, Cole ST. 2001. Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis. Mol Microbiol 40:879–889. [PubMed][CrossRef]
77. Sala C, Forti F, Di Florio E, Canneva F, Milano A, Riccardi G, Ghisotti D. 2003. Mycobacterium tuberculosis FurA autoregulates its own expression. J Bacteriol 185:5357–5362. [PubMed][CrossRef]
78. Zahrt TC, Song J, Siple J, Deretic V. 2001. Mycobacterial FurA is a negative regulator of catalase-peroxidase gene katG. Mol Microbiol 39:1174–1185. [PubMed][CrossRef]
79. Massonet C, Pintens V, Merckx R, Anne J, Lammertyn E, Van Eldere J. 2006. Effect of iron on the expression of sirR and sitABC in biofilm-associated Staphylococcus epidermidis. BMC Microbiol 6:103. [PubMed][CrossRef]
80. Campbell DR, Chapman KE, Waldron KJ, Tottey S, Kendall S, Cavallaro G, Andreini C, Hinds J, Stoker NG, Robinson NJ, Cavet JS. 2007. Mycobacterial cells have dual nickel-cobalt sensors: sequence relationships and metal sites of metal-responsive repressors are not congruent. J Biol Chem 282:32298–32310. [PubMed][CrossRef]
81. Cavet JS, Graham AI, Meng W, Robinson NJ. 2003. A cadmium-lead-sensing ArsR-SmtB repressor with novel sensory sites. Complementary metal discrimination by NmtR and CmtR in a common cytosol. J Biol Chem 278:44560–44566. [PubMed][CrossRef]
82. Canneva F, Branzoni M, Riccardi G, Provvedi R, Milano A. 2005. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J Bacteriol 187:5837–5840. [PubMed][CrossRef]
83. Wagner D, Maser J, Lai B, Cai Z, Barry CE 3rd, Honer Zu Bentrup K, Russell DG, Bermudez LE. 2005. Elemental analysis of Mycobacterium avium-, Mycobacterium tuberculosis-, and Mycobacterium smegmatis-containing phagosomes indicates pathogen-induced microenvironments within the host cell's endosomal system. J Immunol 174:1491–1500. [PubMed][CrossRef]
84. Raimunda D, Long JE, Sassetti CM, Arguello JM. 2012. Role in metal homeostasis of CtpD, a Co(2)(+) transporting P(1B4)-ATPase of Mycobacterium smegmatis. Mol Microbiol 84:1139–1149. [PubMed][CrossRef]
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2014-05-30
2017-12-14

Abstract:

Transition metals are essential constituents of all living organisms, playing crucial structural and catalytic parts in many enzymes and transcription factors. However, transition metals can also be toxic when present in excess. Their uptake and efflux rates must therefore be carefully controlled by biological systems. In this chapter, we summarize the current knowledge about uptake and efflux systems in for mainly three of these metals, namely iron, zinc, and copper. We also propose questions for future research in the field of metallobiology of host-pathogen interactions in tuberculosis.

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FIGURE 1

Carboxymycobactin and mycobactin share a common core structure but differ in the length of the alkyl substitution that determines their polarity and hence solubility. The groups involved in binding of Fe(III) are indicated in bold. doi:10.1128/microbiolspec.MGM2-0012-2013.f1

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0012-2013
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FIGURE 2

When experiencing iron limitation, produces carboxymycobactin (cMB) and mycobactin (MB). MB remains cell associated, although the precise location is not clear. cMB is secreted by a process dependent on the membrane proteins MmpL4 and MmpL5 and requiring the MmpS4 and MmpS5 membrane-associated proteins that function together with their cognate MmpL proteins. Proteins that mediate export of cMB across the outer membrane remain to be discovered. Once secreted, cMB chelates Fe and possibly requires an outer membrane and periplasmic protein to reach the IrtAB importer in the inner membrane. In the cytosol, the FAD binding domain of IrtA may reduce ferric iron to ferrous iron and dissociate the iron-siderophore complex. Released ferrous iron can be utilized and stored in ferritins. Excess iron binds to the regulator IdeR and activates its DNA binding activity. Binding of IdeR to the promoters of siderophore synthesis, secretion, and transport represses the expression of those genes, turning off iron uptake. Meanwhile, IdeR-Fe binding to the promoters of ferritins (ferritin and bacterioferritin) turns on iron storage, thereby preventing iron-mediated toxicity and maintaining iron homeostasis. doi:10.1128/microbiolspec.MGM2-0012-2013.f2

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0012-2013
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P-ATPases in

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0012-2013

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