Skip to main content

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

Abstract

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.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  • 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):e00154

    Article  PubMed Central  PubMed  Google Scholar 

  • Achouiti A et al (2012) Myeloid-related protein-14 contributes to protective immunity in Gram-negative pneumonia derived sepsis. PLoS Pathog 8(10):e1002987

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1476–1478

    Article  PubMed  Google Scholar 

  • Adler J (1975) Chemotaxis in bacteria. Annu Rev Biochem 44:341–356

    Article  CAS  PubMed  Google Scholar 

  • Aguirre JD, Culotta VC (2012) Battles with iron: manganese in oxidative stress protection. J Biol Chem 287(17):13541–13548

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1205–1218

    Article  CAS  PubMed  Google Scholar 

  • 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):844–858

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1061–1069

    Article  CAS  PubMed  Google Scholar 

  • Berry AM, Paton JC (1996) Sequence heterogeneity of PsaA, a 37-kilodalton putative adhesin essential for virulence of Streptococcus pneumoniae. Infect Immun 64(12):5255–5262

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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):689–697

    Article  CAS  PubMed  Google Scholar 

  • 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.e7

  • Blaschitz C, Raffatellu M (2010) Th17 cytokines and the gut mucosal barrier. J Clin Immunol 30(2):196–203

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Botella H et al (2011) Mycobacterial p(1)-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe 10(3):248–259

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):6032–6042

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1695–1704

    Article  CAS  PubMed  Google Scholar 

  • 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):18089–18100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):17804–17817

    Article  PubMed Central  PubMed  Google Scholar 

  • CDC (2013) Antibiotic resistance threats in the United States, 2013. Center for Disease Control and Prevention. http://www.cdc.gov/drugresistance/threat-report-2013/index.html. Accessed 27 March 2014

  • Cellier MF, Courville P, Campion C (2007) Nramp1 phagocyte intracellular metal withdrawal defense. Microbes Infect 9(14–15):1662–1670

    Article  CAS  PubMed  Google Scholar 

  • 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):970–982

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):3898–3903

    PubMed Central  CAS  PubMed  Google Scholar 

  • Clohessy PA, Golden BE (1995) Calprotectin-mediated zinc chelation as a biostatic mechanism in host defence. Scand J Immunol 42(5):551–556

    Article  CAS  PubMed  Google Scholar 

  • Corbin BD et al (2008) Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 319(5865):962–965

    Article  CAS  PubMed  Google Scholar 

  • Cotruvo JA, Stubbe J (2011) Escherichia coli class Ib ribonucleotide reductase contains a dimanganese(III)-tyrosyl radical cofactor in vivo. Biochemistry 50(10):1672–1681

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Couñago RM, McDevitt CA, Ween MP, Kobe B (2012) Prokaryotic substrate-binding proteins as targets for antimicrobial therapies. Curr Drug Targets 13(11):1400–1410

    Article  PubMed  Google Scholar 

  • Couñago RM et al (2014) Imperfect coordination chemistry facilitates metal ion release in the Psa permease. Nat Chem Biol 10(1):35–41

    Article  PubMed  Google Scholar 

  • 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):3841–3846

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):317–364

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Diep BA et al (2014) Identifying potential therapeutic targets of methicillin-resistant Staphylococcus aureus through in vivo proteomic analysis. J Infect Dis 209(10):1533–1541

    Article  CAS  PubMed  Google Scholar 

  • 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):10567–10572

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):990–996

    Article  CAS  PubMed  Google Scholar 

  • 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):e89427

    Article  PubMed Central  PubMed  Google Scholar 

  • Gebhardt C, Nemeth J, Angel P, Hess J (2006) S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol 72(11):1622–1631

    Article  CAS  PubMed  Google Scholar 

  • 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):3971–3974

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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):18377–18389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):3429–3445

    Article  CAS  PubMed  Google Scholar 

  • 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):1229–1238

    Article  CAS  PubMed  Google Scholar 

  • Guilbert JJ (2003) The world health report 2002—reducing risks, promoting healthy life. Educ Health (Abingdon) 16(2):230

    Article  CAS  Google Scholar 

  • Haase H, Rink L (2009) Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr 29:133–152

    Article  CAS  PubMed  Google Scholar 

  • 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):775–787

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Higgins CF (1992) ABC transporters: from microorganisms to man. Annu Rev Cell Biol 8:67–113

    Article  CAS  PubMed  Google Scholar 

  • Hood MI, Skaar EP (2012) Nutritional immunity: transition metals at the pathogen–host interface. Nat Rev Microbiol 10(8):525–537

    Article  CAS  PubMed  Google Scholar 

  • 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):e1003068

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1269–1286

    Article  CAS  PubMed  Google Scholar 

  • Hsu K et al (2009) Anti-infective protective properties of S100 calgranulins. Antiinflamm Antiallergy Agents Med Chem 8(4):290–305

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):630–641

    Article  CAS  PubMed  Google Scholar 

  • Imlay JA (2013) The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat Rev Microbiol 11(7):443–454

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Irving H, Williams RJP (1953) The stability of transition-metal complexes. J Chem Soc 3:3192–3210

    Article  Google Scholar 

  • 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):1237–1248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1146–1155

    Article  CAS  PubMed  Google Scholar 

  • 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):2656–2664

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Karavolos MH, Horsburgh MJ, Ingham E, Foster SJ (2003) Role and regulation of the superoxide dismutases of Staphylococcus aureus. Microbiology 149(Pt 10):2749–2758

    Article  CAS  PubMed  Google Scholar 

  • Keele BB Jr, McCord JM, Fridovich I (1970) Superoxide dismutase from Escherichia coli B. A new manganese-containing enzyme. J Biol Chem 245(22):6176–6181

    CAS  PubMed  Google Scholar 

  • Kehl-Fie TE, Skaar EP (2010) Nutritional immunity beyond iron: a role for manganese and zinc. Curr Opin Chem Biol 14(2):218–224

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):158–164

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):3395–3405

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):887–898

    Article  PubMed  Google Scholar 

  • 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:CD005978

    PubMed  Google Scholar 

  • 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):1553–1561

    Article  CAS  PubMed  Google Scholar 

  • 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):628–633

    Article  CAS  PubMed  Google Scholar 

  • 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):2300–2304

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lemire JA, Harrison JJ, Turner RJ (2013) Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 11(6):371–384

    Article  CAS  PubMed  Google Scholar 

  • Lewis VG, Ween MP, McDevitt CA (2012) The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma 249(4):919–942

    Article  CAS  PubMed  Google Scholar 

  • 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):1358–1366

    Article  CAS  PubMed  Google Scholar 

  • 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):3569–3576

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lippard SJ, Berg JM (1994) Principles of bioinorganic chemistry. University Science Books, Mill Valley

    Google Scholar 

  • Lisher JP, Giedroc DP (2013) Manganese acquisition and homeostasis at the host–pathogen interface. Front Cell Infect Microbiol 3:91

  • 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):594–606

    Article  CAS  PubMed  Google Scholar 

  • Ma Z, Jacobsen FE, Giedroc DP (2009) Coordination chemistry of bacterial metal transport and sensing. Chem Rev 109(10):4644–4681

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):1483–1491

    CAS  PubMed  Google Scholar 

  • 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):889–901

    Article  CAS  PubMed  Google Scholar 

  • 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):e1002357

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Moroz OV et al (2003) Structure of the human S100A12–copper complex: implications for host–parasite defence. Acta Crystallogr D 59(Pt 5):859–867

    Article  CAS  PubMed  Google Scholar 

  • 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):536–551

    Article  CAS  PubMed  Google Scholar 

  • 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):3685–3692

    CAS  PubMed  Google Scholar 

  • Nevo Y, Nelson N (2006) The NRAMP family of metal-ion transporters. Biochim Biophys Acta 1763(7):609–620

    Article  CAS  PubMed  Google Scholar 

  • Ogunniyi AD et al (2010) Central role of manganese in regulation of stress responses, physiology, and metabolism in Streptococcus pneumoniae. J Bacteriol 192(17):4489–4497

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Oldham ML, Khare D, Quiocho FA, Davidson AL, Chen J (2007) Crystal structure of a catalytic intermediate of the maltose transporter. Nature 450(7169):515–521

    Article  CAS  PubMed  Google Scholar 

  • 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):1500–1508

    Article  CAS  PubMed  Google Scholar 

  • 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):5967–5975

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Papp-Wallace KM, Maguire ME (2006) Manganese transport and the role of manganese in virulence. Annu Rev Microbiol 60:187–209

    Article  CAS  PubMed  Google Scholar 

  • 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):834–851

    Article  CAS  PubMed  Google Scholar 

  • Prasad AS (2003) Zinc deficiency. BMJ 326(7386):409–410

    Article  PubMed Central  PubMed  Google Scholar 

  • 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):151–164

    Article  CAS  PubMed  Google Scholar 

  • 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):5402–5407

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):6184–6190

    Article  CAS  PubMed  Google Scholar 

  • Sutcliffe IC, Russell RR (1995) Lipoproteins of Gram-positive bacteria. J Bacteriol 177(5):1123–1128

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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):e1000639

    Article  PubMed Central  PubMed  Google Scholar 

  • 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):1079–1084

    Article  PubMed  Google Scholar 

  • Valderas MW, Hart ME (2001) Identification and characterization of a second superoxide dismutase gene (sodM) from Staphylococcus aureus. J Bacteriol 183(11):3399–3407

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):e1002261

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Waldron KJ, Robinson NJ (2009) How do bacterial cells ensure that metalloproteins get the correct metal? Nat Rev Microbiol 7(1):25–35

    Article  CAS  PubMed  Google Scholar 

  • 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):33949–33956

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • WHO (2003) WHO position paper—Streptococcus pneumoniae. WER 78:110–118

    Google Scholar 

  • WHO (2014) Antimicrobial resistance global report on surveillance. World Health Organization, Geneva, Switzerland

  • 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):5073–5080

    Article  PubMed  Google Scholar 

  • Williams RJ (2002) The fundamental nature of life as a chemical system: the part played by inorganic elements. J Inorg Biochem 88(3–4):241–250

    Article  CAS  PubMed  Google Scholar 

  • Wu HJ et al (2010) Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae. J Proteomics 73(5):899–916

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):2819–2826

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):5522–5525

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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–S18

    Article  PubMed  Google Scholar 

  • Zheng B et al (2011) Insight into the interaction of metal ions with TroA from Streptococcus suis. PLoS ONE 6(5):e19510

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Christopher A. McDevitt or Thomas E. Kehl-Fie.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Morey, J.R., McDevitt, C.A. & Kehl-Fie, T.E. Host-imposed manganese starvation of invading pathogens: two routes to the same destination. Biometals 28, 509–519 (2015). https://doi.org/10.1007/s10534-015-9850-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-015-9850-z

Keywords

  • ABC transporter
  • Manganese
  • Zinc
  • Nutritional immunity
  • Calprotectin
  • Infection