, Volume 28, Issue 3, pp 509–519 | Cite as

Host-imposed manganese starvation of invading pathogens: two routes to the same destination

  • Jacqueline R. Morey
  • Christopher A. McDevitt
  • Thomas E. Kehl-Fie


During infection invading pathogens must acquire all essential nutrients, including first row transition metals, from the host. To combat invaders, the host exploits this fact and restricts the availability of these nutrients using a defense mechanism known as nutritional immunity. While iron sequestration is the most well-known aspect of this defense, recent work has revealed that the host restricts the availability of other essential elements, notably manganese (Mn), during infection. Furthermore, these studies have revealed that the host utilizes multiple strategies that extend beyond metal sequestration to prevent bacteria from obtaining these metals. This review will discuss the mechanisms by which bacteria attempt to obtain the essential first row transition metal ion Mn during infection, and the approaches utilized by the host to prevent this occurrence. In addition, this review will discuss the impact of host-imposed Mn starvation on invading bacteria.


ABC transporter Manganese Zinc Nutritional immunity Calprotectin Infection 



We apologize to our colleagues whose work we were unable to cite due to length restrictions. J.R.M. is supported by an Australian Postgraduate Award. This work was supported by the Australian Research Council Grants DP120103957 and DP150104515 to C.A.M., the National Health and Medical Research Council Project Grants 1022240 and 1080784 to C.A.M., and a K22 AI104805 from the National Institutes of Health as well as by Research Grant No. 5-FY15-30 from the March of Dimes Foundation to T.E.K. This work is solely the responsibility of the authors and does not reflect the views of the National Institutes of Health.

Conflict of interest

The authors declare no competing financial interests.


  1. Abate F, Malito E, Cozzi R, Lo Surdo P, Maione D, Bottomley MJ (2014) Apo, Zn2+-bound and Mn2+-bound structures reveal ligand-binding properties of SitA from the pathogen Staphylococcus pseudintermedius. Biosci Rep 34(6):e00154CrossRefPubMedCentralPubMedGoogle Scholar
  2. Achouiti A et al (2012) Myeloid-related protein-14 contributes to protective immunity in Gram-negative pneumonia derived sepsis. PLoS Pathog 8(10):e1002987CrossRefPubMedCentralPubMedGoogle Scholar
  3. Adir N, Rukhman V, Brumshtein B, Anati R (2002) Preliminary X-ray crystallographic analysis of a soluble form of MntC, a periplasmic manganese-binding component of an ABC-type Mn transporter from Synechocystis sp. PCC 6803. Acta Crystallogr D 58(Pt 9):1476–1478CrossRefPubMedGoogle Scholar
  4. Adler J (1975) Chemotaxis in bacteria. Annu Rev Biochem 44:341–356CrossRefPubMedGoogle Scholar
  5. Aguirre JD, Culotta VC (2012) Battles with iron: manganese in oxidative stress protection. J Biol Chem 287(17):13541–13548CrossRefPubMedCentralPubMedGoogle Scholar
  6. Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM (2008) Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem 13(8):1205–1218CrossRefPubMedGoogle Scholar
  7. Anjem A, Varghese S, Imlay JA (2009) Manganese import is a key element of the OxyR response to hydrogen peroxide in Escherichia coli. Mol Microbiol 72(4):844–858CrossRefPubMedCentralPubMedGoogle Scholar
  8. Banerjee S, Wei B, Bhattacharyya-Pakrasi M, Pakrasi HB, Smith TJ (2003) Structural determinants of metal specificity in the zinc transport protein ZnuA from Synechocystis 6803. J Mol Biol 333(5):1061–1069CrossRefPubMedGoogle Scholar
  9. Berry AM, Paton JC (1996) Sequence heterogeneity of PsaA, a 37-kilodalton putative adhesin essential for virulence of Streptococcus pneumoniae. Infect Immun 64(12):5255–5262PubMedCentralPubMedGoogle Scholar
  10. Bhutta ZA et al (1999) Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators’ Collaborative Group. J Pediatr 135(6):689–697CrossRefPubMedGoogle Scholar
  11. Bianchi M, Niemiec MJ, Siler U, Urban CF, Reichenbach J (2011) Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol 127(5):1243–1252.e7Google Scholar
  12. Blaschitz C, Raffatellu M (2010) Th17 cytokines and the gut mucosal barrier. J Clin Immunol 30(2):196–203CrossRefPubMedCentralPubMedGoogle Scholar
  13. Botella H et al (2011) Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe 10(3):248–259CrossRefPubMedCentralPubMedGoogle Scholar
  14. Boyer E, Bergevin I, Malo D, Gros P, Cellier MF (2002) Acquisition of Mn(II) in addition to Fe(II) is required for full virulence of Salmonella enterica serovar Typhimurium. Infect Immun 70(11):6032–6042CrossRefPubMedCentralPubMedGoogle Scholar
  15. Brodersen DE, Nyborg J, Kjeldgaard M (1999) Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states. Biochemistry 38(6):1695–1704CrossRefPubMedGoogle Scholar
  16. Brophy MB, Hayden JA, Nolan EM (2012) Calcium ion gradients modulate the zinc affinity and antibacterial activity of human calprotectin. J Am Chem Soc 134(43):18089–18100CrossRefPubMedCentralPubMedGoogle Scholar
  17. Brophy MB, Nakashige TG, Gaillard A, Nolan EM (2013) Contributions of the S100A9 C-terminal tail to high-affinity Mn(II) chelation by the host-defense protein human calprotectin. J Am Chem Soc 135(47):17804–17817CrossRefPubMedCentralPubMedGoogle Scholar
  18. CDC (2013) Antibiotic resistance threats in the United States, 2013. Center for Disease Control and Prevention. Accessed 27 March 2014
  19. Cellier MF, Courville P, Campion C (2007) Nramp1 phagocyte intracellular metal withdrawal defense. Microbes Infect 9(14–15):1662–1670CrossRefPubMedGoogle Scholar
  20. Chandra BR, Yogavel M, Sharma A (2007) Structural analysis of ABC-family periplasmic zinc binding protein provides new insights into mechanism of ligand uptake and release. J Mol Biol 367(4):970–982CrossRefPubMedCentralPubMedGoogle Scholar
  21. Clements MO, Watson SP, Foster SJ (1999) Characterization of the major superoxide dismutase of Staphylococcus aureus and its role in starvation survival, stress resistance, and pathogenicity. J Bacteriol 181(13):3898–3903PubMedCentralPubMedGoogle Scholar
  22. Clohessy PA, Golden BE (1995) Calprotectin-mediated zinc chelation as a biostatic mechanism in host defence. Scand J Immunol 42(5):551–556CrossRefPubMedGoogle Scholar
  23. Corbin BD et al (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965CrossRefPubMedGoogle Scholar
  24. Cotruvo JA, Stubbe J (2011) Escherichia coli class Ib ribonucleotide reductase contains a dimanganese(III)-tyrosyl radical cofactor in vivo. Biochemistry 50(10):1672–1681CrossRefPubMedCentralPubMedGoogle Scholar
  25. Couñago RM, McDevitt CA, Ween MP, Kobe B (2012) Prokaryotic substrate-binding proteins as targets for antimicrobial therapies. Curr Drug Targets 13(11):1400–1410CrossRefPubMedGoogle Scholar
  26. Couñago RM et al (2014) Imperfect coordination chemistry facilitates metal ion release in the Psa permease. Nat Chem Biol 10(1):35–41CrossRefPubMedGoogle Scholar
  27. Damo SM 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 USA 110(10):3841–3846CrossRefPubMedCentralPubMedGoogle Scholar
  28. Davidson AL, Dassa E, Orelle C, Chen J (2008) Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol Mol Biol Rev 72(2):317–364CrossRefPubMedCentralPubMedGoogle Scholar
  29. Diep BA et al (2014) Identifying potential therapeutic targets of methicillin-resistant Staphylococcus aureus through in vivo proteomic analysis. J Infect Dis 209(10):1533–1541CrossRefPubMedGoogle Scholar
  30. Dupont CL, Butcher A, Valas RE, Bourne PE, Caetano-Anolles G (2010) History of biological metal utilization inferred through phylogenomic analysis of protein structures. Proc Natl Acad Sci USA 107(23):10567–10572CrossRefPubMedCentralPubMedGoogle Scholar
  31. Ehrnstorfer IA, Geertsma ER, Pardon E, Steyaert J, Dutzler R (2014) Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport. Nat Struct Mol Biol 21(11):990–996CrossRefPubMedGoogle Scholar
  32. Eijkelkamp BA, Morey JR, Ween MP, Ong CL, McEwan AG, Paton JC, McDevitt CA (2014) Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae. PLoS ONE 9(2):e89427CrossRefPubMedCentralPubMedGoogle Scholar
  33. Gebhardt C, Nemeth J, Angel P, Hess J (2006) S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol 72(11):1622–1631CrossRefPubMedGoogle Scholar
  34. Gilson E, Alloing G, Schmidt T, Claverys JP, Dudler R, Hofnung M (1988) Evidence for high affinity binding-protein dependent transport systems in Gram-positive bacteria and in Mycoplasma. EMBO J 7(12):3971–3974PubMedCentralPubMedGoogle Scholar
  35. Graham AI et al (2009) Severe zinc depletion of Escherichia coli: roles for high affinity zinc binding by ZinT, zinc transport and zinc-independent proteins. J Biol Chem 284(27):18377–18389CrossRefPubMedCentralPubMedGoogle Scholar
  36. Gribenko A et al (2013) Three-dimensional structure and biophysical characterization of Staphylococcus aureus cell surface antigen-manganese transporter MntC. J Mol Biol 425(18):3429–3445CrossRefPubMedGoogle Scholar
  37. Groot MN, Klaassens E, de Vos WM, Delcour J, Hols P, Kleerebezem M (2005) Genome-based in silico detection of putative manganese transport systems in Lactobacillus plantarum and their genetic analysis. Microbiology 151(Pt 4):1229–1238CrossRefPubMedGoogle Scholar
  38. Guilbert JJ (2003) The world health report 2002—reducing risks, promoting healthy life. Educ Health (Abingdon) 16(2):230CrossRefGoogle Scholar
  39. Haase H, Rink L (2009) Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr 29:133–152CrossRefPubMedGoogle Scholar
  40. Hayden JA, Brophy MB, Cunden LS, Nolan EM (2013) High-affinity manganese coordination by human calprotectin is calcium-dependent and requires the histidine-rich site formed at the dimer interface. J Am Chem Soc 135(2):775–787CrossRefPubMedCentralPubMedGoogle Scholar
  41. Higgins CF (1992) ABC transporters: from microorganisms to man. Annu Rev Cell Biol 8:67–113CrossRefPubMedGoogle Scholar
  42. Hood MI, Skaar EP (2012) Nutritional immunity: transition metals at the pathogen–host interface. Nat Rev Microbiol 10(8):525–537CrossRefPubMedGoogle Scholar
  43. Hood MI et al (2012) Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration. PLoS Pathog 8(12):e1003068CrossRefPubMedCentralPubMedGoogle Scholar
  44. Horsburgh MJ, Wharton SJ, Cox AG, Ingham E, Peacock S, Foster SJ (2002) MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44(5):1269–1286CrossRefPubMedGoogle Scholar
  45. Hsu K et al (2009) Anti-infective protective properties of S100 calgranulins. Antiinflamm Antiallergy Agents Med Chem 8(4):290–305CrossRefPubMedCentralPubMedGoogle Scholar
  46. Ilari A, Alaleona F, Petrarca P, Battistoni A, Chiancone E (2011) The X-ray structure of the zinc transporter ZnuA from Salmonella enterica discloses a unique triad of zinc-coordinating histidines. J Mol Biol 409(4):630–641CrossRefPubMedGoogle Scholar
  47. Imlay JA (2013) The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat Rev Microbiol 11(7):443–454CrossRefPubMedCentralPubMedGoogle Scholar
  48. Irving H, Williams RJP (1953) The stability of transition-metal complexes. J Chem Soc 3:3192–3210CrossRefGoogle Scholar
  49. Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, 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(9):1237–1248CrossRefPubMedCentralPubMedGoogle Scholar
  50. Janakiraman A, Slauch JM (2000) The putative iron transport system SitABCD encoded on SPI1 is required for full virulence of Salmonella typhimurium. Mol Microbiol 35(5):1146–1155CrossRefPubMedGoogle Scholar
  51. Janulczyk R, Ricci S, Bjorck L (2003) MtsABC is important for manganese and iron transport, oxidative stress resistance, and virulence of Streptococcus pyogenes. Infect Immun 71(5):2656–2664CrossRefPubMedCentralPubMedGoogle Scholar
  52. Karavolos MH, Horsburgh MJ, Ingham E, Foster SJ (2003) Role and regulation of the superoxide dismutases of Staphylococcus aureus. Microbiology 149(Pt 10):2749–2758CrossRefPubMedGoogle Scholar
  53. Keele BB Jr, McCord JM, Fridovich I (1970) Superoxide dismutase from Escherichia coli B. A new manganese-containing enzyme. J Biol Chem 245(22):6176–6181PubMedGoogle Scholar
  54. Kehl-Fie TE, Skaar EP (2010) Nutritional immunity beyond iron: a role for manganese and zinc. Curr Opin Chem Biol 14(2):218–224CrossRefPubMedCentralPubMedGoogle Scholar
  55. Kehl-Fie TE et al (2011) Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. Cell Host Microbe 10(2):158–164CrossRefPubMedCentralPubMedGoogle Scholar
  56. Kehl-Fie TE et al (2013) MntABC and MntH contribute to systemic Staphylococcus aureus infection by competing with calprotectin for nutrient manganese. Infect Immun 81(9):3395–3405CrossRefPubMedCentralPubMedGoogle Scholar
  57. Korndorfer IP, Brueckner F, Skerra A (2007) The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins. J Mol Biol 370(5):887–898CrossRefPubMedGoogle Scholar
  58. Lassi ZS, Haider BA, Bhutta ZA (2010) Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 12:CD005978PubMedGoogle Scholar
  59. Lawrence MC, Pilling PA, Epa VC, Berry AM, Ogunniyi AD, Paton JC (1998) The crystal structure of pneumococcal surface antigen PsaA reveals a metal-binding site and a novel structure for a putative ABC-type binding protein. Structure 6(12):1553–1561CrossRefPubMedGoogle Scholar
  60. Lee YH, Deka RK, Norgard MV, Radolf JD, Hasemann CA (1999) Treponema pallidum TroA is a periplasmic zinc-binding protein with a helical backbone. Nat Struct Biol 6(7):628–633CrossRefPubMedGoogle Scholar
  61. Lee YH, Dorwart MR, Hazlett KR, Deka RK, Norgard MV, Radolf JD, Hasemann CA (2002) The crystal structure of Zn(II)-free Treponema pallidum TroA, a periplasmic metal-binding protein, reveals a closed conformation. J Bacteriol 184(8):2300–2304CrossRefPubMedCentralPubMedGoogle Scholar
  62. Lemire JA, Harrison JJ, Turner RJ (2013) Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 11(6):371–384CrossRefPubMedGoogle Scholar
  63. Lewis VG, Ween MP, McDevitt CA (2012) The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma 249(4):919–942CrossRefPubMedGoogle Scholar
  64. Li H, Jogl G (2007) Crystal structure of the zinc-binding transport protein ZnuA from Escherichia coli reveals an unexpected variation in metal coordination. J Mol Biol 368(5):1358–1366CrossRefPubMedGoogle Scholar
  65. Lim KH et al (2008) Metal binding specificity of the MntABC permease of Neisseria gonorrhoeae and its influence on bacterial growth and interaction with cervical epithelial cells. Infect Immun 76(8):3569–3576CrossRefPubMedCentralPubMedGoogle Scholar
  66. Lippard SJ, Berg JM (1994) Principles of bioinorganic chemistry. University Science Books, Mill ValleyGoogle Scholar
  67. Lisher JP, Giedroc DP (2013) Manganese acquisition and homeostasis at the host–pathogen interface. Front Cell Infect Microbiol 3:91Google Scholar
  68. Loisel E et al (2008) AdcAII, a new pneumococcal Zn-binding protein homologous with ABC transporters: biochemical and structural analysis. J Mol Biol 381(3):594–606CrossRefPubMedGoogle Scholar
  69. Ma Z, Jacobsen FE, Giedroc DP (2009) Coordination chemistry of bacterial metal transport and sensing. Chem Rev 109(10):4644–4681CrossRefPubMedCentralPubMedGoogle Scholar
  70. Marra A, Lawson S, Asundi JS, Brigham D, Hromockyj AE (2002) In vivo characterization of the psa genes from Streptococcus pneumoniae in multiple models of infection. Microbiology 148(Pt 5):1483–1491PubMedGoogle Scholar
  71. McAllister LJ, Tseng HJ, Ogunniyi AD, Jennings MP, McEwan AG, Paton JC (2004) Molecular analysis of the psa permease complex of Streptococcus pneumoniae. Mol Microbiol 53(3):889–901CrossRefPubMedGoogle Scholar
  72. 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(11):e1002357CrossRefPubMedCentralPubMedGoogle Scholar
  73. Moroz OV et al (2003) Structure of the human S100A12–copper complex: implications for host–parasite defence. Acta Crystallogr D 59(Pt 5):859–867CrossRefPubMedGoogle Scholar
  74. Moroz OV, Blagova EV, Wilkinson AJ, Wilson KS, Bronstein IB (2009) The crystal structures of human S100A12 in apo form and in complex with zinc: new insights into S100A12 oligomerisation. J Mol Biol 391(3):536–551CrossRefPubMedGoogle Scholar
  75. Neu HC, Heppel LA (1965) The release of enzymes from Escherichia coli by osmotic shock and during the formation of spheroplasts. J Biol Chem 240(9):3685–3692PubMedGoogle Scholar
  76. Nevo Y, Nelson N (2006) The NRAMP family of metal-ion transporters. Biochim Biophys Acta 1763(7):609–620CrossRefPubMedGoogle Scholar
  77. Ogunniyi AD et al (2010) Central role of manganese in regulation of stress responses, physiology, and metabolism in Streptococcus pneumoniae. J Bacteriol 192(17):4489–4497CrossRefPubMedCentralPubMedGoogle Scholar
  78. Oldham ML, Khare D, Quiocho FA, Davidson AL, Chen J (2007) Crystal structure of a catalytic intermediate of the maltose transporter. Nature 450(7169):515–521CrossRefPubMedGoogle Scholar
  79. Ong CL, Gillen CM, Barnett TC, Walker MJ, McEwan AG (2014) An antimicrobial role for zinc in innate immune defense against group A Streptococcus. J Infect Dis 209(10):1500–1508CrossRefPubMedGoogle Scholar
  80. Paik S, Brown A, Munro CL, Cornelissen CN, Kitten T (2003) The sloABCR operon of Streptococcus mutans encodes an Mn and Fe transport system required for endocarditis virulence and its Mn-dependent repressor. J Bacteriol 185(20):5967–5975CrossRefPubMedCentralPubMedGoogle Scholar
  81. Papp-Wallace KM, Maguire ME (2006) Manganese transport and the role of manganese in virulence. Annu Rev Microbiol 60:187–209CrossRefPubMedGoogle Scholar
  82. Plumptre CD et al (2014) AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae. Mol Microbiol 91(4):834–851CrossRefPubMedGoogle Scholar
  83. Prasad AS (2003) Zinc deficiency. BMJ 326(7386):409–410CrossRefPubMedCentralPubMedGoogle Scholar
  84. Shumaker DK, Vann LR, Goldberg MW, Allen TD, Wilson KL (1998) TPEN, a Zn2+/Fe2+ chelator with low affinity for Ca2+, inhibits lamin assembly, destabilizes nuclear architecture and may independently protect nuclei from apoptosis in vitro. Cell Calcium 23(2–3):151–164CrossRefPubMedGoogle Scholar
  85. Sobota JM, Imlay JA (2011) Iron enzyme ribulose-5-phosphate 3-epimerase in Escherichia coli is rapidly damaged by hydrogen peroxide but can be protected by manganese. Proc Natl Acad Sci USA 108(13):5402–5407CrossRefPubMedCentralPubMedGoogle Scholar
  86. Sun X, Baker HM, Ge R, Sun H, He QY, Baker EN (2009) Crystal structure and metal binding properties of the lipoprotein MtsA, responsible for iron transport in Streptococcus pyogenes. Biochemistry 48(26):6184–6190CrossRefPubMedGoogle Scholar
  87. Sutcliffe IC, Russell RR (1995) Lipoproteins of Gram-positive bacteria. J Bacteriol 177(5):1123–1128PubMedCentralPubMedGoogle Scholar
  88. Urban CF et al (2009) Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog 5(10):e1000639CrossRefPubMedCentralPubMedGoogle Scholar
  89. Valavi E, Hakimzadeh M, Shamsizadeh A, Aminzadeh M, Alghasi A (2011) The efficacy of zinc supplementation on outcome of children with severe pneumonia. A randomized double-blind placebo-controlled clinical trial. Indian J Pediatr 78(9):1079–1084CrossRefPubMedGoogle Scholar
  90. Valderas MW, Hart ME (2001) Identification and characterization of a second superoxide dismutase gene (sodM) from Staphylococcus aureus. J Bacteriol 183(11):3399–3407CrossRefPubMedCentralPubMedGoogle Scholar
  91. Veyrier FJ, Boneca IG, Cellier MF, Taha MK (2011) A novel metal transporter mediating manganese export (MntX) regulates the Mn to Fe intracellular ratio and Neisseria meningitidis virulence. PLoS Pathog 7(9):e1002261CrossRefPubMedCentralPubMedGoogle Scholar
  92. Waldron KJ, Robinson NJ (2009) How do bacterial cells ensure that metalloproteins get the correct metal? Nat Rev Microbiol 7(1):25–35CrossRefPubMedGoogle Scholar
  93. 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(49):33949–33956CrossRefPubMedCentralPubMedGoogle Scholar
  94. WHO (2003) WHO position paper—Streptococcus pneumoniae. WER 78:110–118Google Scholar
  95. WHO (2014) Antimicrobial resistance global report on surveillance. World Health Organization, Geneva, SwitzerlandGoogle Scholar
  96. Wichgers Schreur PJ, Rebel JM, Smits MA, van Putten JP, Smith HE (2011) TroA of Streptococcus suis is required for manganese acquisition and full virulence. J Bacteriol 193(19):5073–5080CrossRefPubMedGoogle Scholar
  97. Williams RJ (2002) The fundamental nature of life as a chemical system: the part played by inorganic elements. J Inorg Biochem 88(3–4):241–250CrossRefPubMedGoogle Scholar
  98. Wu HJ et al (2010) Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae. J Proteomics 73(5):899–916CrossRefPubMedCentralPubMedGoogle Scholar
  99. Yesilkaya H, Kadioglu A, Gingles N, Alexander JE, Mitchell TJ, Andrew PW (2000) Role of manganese-containing superoxide dismutase in oxidative stress and virulence of Streptococcus pneumoniae. Infect Immun 68(5):2819–2826CrossRefPubMedCentralPubMedGoogle Scholar
  100. Zaharik ML et al (2004) The Salmonella enterica serovar typhimurium divalent cation transport systems MntH and SitABCD are essential for virulence in an Nramp1G169 murine typhoid model. Infect Immun 72(9):5522–5525CrossRefPubMedCentralPubMedGoogle Scholar
  101. Zaidi AK, Thaver D, Ali SA, Khan TA (2009) Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J 28(1 Suppl):S10–S18CrossRefPubMedGoogle Scholar
  102. Zheng B et al (2011) Insight into the interaction of metal ions with TroA from Streptococcus suis. PLoS ONE 6(5):e19510CrossRefPubMedCentralPubMedGoogle Scholar

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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Research Centre for Infectious Diseases, School of Molecular and Biomedical ScienceUniversity of AdelaideAdelaideAustralia
  2. 2.Department of MicrobiologyUniversity of Illinois Urbana-ChampaignUrbanaUSA

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