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Salmonella–Macrophage Interactions upon Manganese Supplementation

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Abstract

Various studies indicate the role of manganese (Mn) in the virulence of pathogens. Salmonella is an intracellular pathogen which is able to multiply within the macrophages. The present study was therefore, designed to assess the effect of Mn supplementation on Salmonella–macrophage interactions particularly in reference to Salmonella virulence and macrophage functions. A 50-fold decrease in the lethal dose 50 (LD50) of Salmonella typhimurium was observed when mice were infected with Salmonella grown in the presence of Mn as compared to the LD50 in the absence of Mn indicating an increase in the virulence of the organism. A significant increase was observed in the levels of superoxide dismutase (SOD) of S. typhimurium grown in presence of manganese. Upon Mn supplementation, macrophage functions were also found to be altered. Decreased phagocytic activity of macrophages interacted with Salmonella was observed in presence of Mn as compared to the activity in the absence of Mn. A significant increase was observed in the extent of lipid peroxidation along with significant decreases in the activities of SOD and catalase as well as nitrite levels of macrophages interacted with S. typhimurium upon supplementation with Mn. These observations indicate that Mn supplementation might have increased the expression of Mn transporters in Salmonella resulting in increased levels of its superoxide dismutase. The altered Salmonella function in turn might have been responsible for inhibiting phagocytosis and impairing the balance between the oxidant and antioxidant profile of macrophages, thus protecting itself by exhibiting exalted virulence.

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References

  1. Smith H (1998) What happens to bacterial pathogens in vivo? Trends Microbiol 6:239–243

    Article  CAS  PubMed  Google Scholar 

  2. Sood S, Rishi P, Vohra H, Sharma S, Ganguly NK (2005) Cellular immune response induced by Salmonella enterica serotype Typhi iron-regulated outer-membrane proteins at peripheral and mucosal levels. J Med Microbiol 54:815–821

    Article  CAS  PubMed  Google Scholar 

  3. Vidal SM, Pinner E, Lepage P, Gauthier S, Gros P (1996) Natural resistance to intracellular infections: Nramp1 encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nramp1 D169) mouse strains. J Immunol 157:3559–3568

    CAS  PubMed  Google Scholar 

  4. Groisman EA (2001) The pleiotropic two-component regulatory system PhoP-PhoQ. J Bacteriol 183:1835–1842

    Article  CAS  PubMed  Google Scholar 

  5. Zaharik ML, Vallance BA, Puente JL, Gros P, Finlay BB (2002) Host–pathogen interactions: host resistance factor Nramp1 up-regulates the expression of Salmonella pathogenicity island-2 virulence genes. Proc Natl Acad Sci U S A 99:15705–15710

    Article  CAS  PubMed  Google Scholar 

  6. Braun V, Killmann H (1999) Bacterial solutions to the iron supply problem. Trends Biochem Sci 24:104–109

    Article  CAS  PubMed  Google Scholar 

  7. Hantke K, Braun V (2000) The art of keeping low and high iron concentrations in balance. In: Storz G, Henge-Aronis R (eds) Bacterial stress responses. ASM, VA, pp 275–288

    Google Scholar 

  8. Posey JE, Gherardini FC (2000) Lack of a role for iron in the Lyme disease pathogen. Science 288:1651–1653

    Article  CAS  PubMed  Google Scholar 

  9. Jakubovics NS, Jenkinson HF (2001) Out of the iron age: new insights into the critical role of manganese homeostasis in bacteria. Microbiology 147:1709–1718

    CAS  PubMed  Google Scholar 

  10. Silver S, Lusk JE (1987) Bacterial magnesium, manganese and zinc transport. In: Rosen BP, Silver S (eds) Ion transport in prokaryotes. Academic, London, pp 165–180

    Google Scholar 

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

    Article  Google Scholar 

  12. Zaharik ML, Cullen VL, Fung AM, Libby SJ, Kujat CSL (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 72:5522–5525

    Article  CAS  PubMed  Google Scholar 

  13. Zhou D, Hardt WD, Galan JE (1999) Salmonella typhimurium encodes a putative iron transport system within the centisome 63 pathogenicity island. Infect Immun 67:1974–1981

    CAS  PubMed  Google Scholar 

  14. Kehres DG, Zaharik ML, Finlay BB, Maguire ME (2000) The NRAMP proteins of Salmonella typhimurium and Escherichia coli are selective manganese transporters involved in the response to reactive oxygen. Mol Microbiol 36:1085–1100

    Article  CAS  PubMed  Google Scholar 

  15. Zaharik ML (2003) Host-pathogen interactions: the impact of Nramp1 on Salmonella enterica serovar Typhimurium virulence gene expression. PhD Thesis, University of British Columbia, Vancouver, Canada

  16. Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497

    Google Scholar 

  17. Tabaraie B, Sharma BK, Rishi nee Sharma P, Sehgal R, Ganguly NK (1994) Evaluation of Salmonella porins as a broad spectrum vaccine candidate. Microbiol Immunol 38:553–559

    CAS  PubMed  Google Scholar 

  18. Tiwari RP, Gupta W, Rishi P (1998) Immunobiology of lipopolysaccharide (LPS) and LPS-derived immunoconjugates vaccinate mice against Salmonella typhimurium. Microbiol Immunol 42:1–5

    CAS  PubMed  Google Scholar 

  19. Kono Y (1978) Generation of superoxide radical during autooxidation of hydroxylamine and an assay of superoxide dismutase. Arch Biochem Biophys 186:189–195

    Article  CAS  PubMed  Google Scholar 

  20. Allen PM, Fisher D, Saunders JR, Hart CA (1987) The role of capsular polysaccharide K21b of Klebsiella and of the structurally related colanic-acid polysaccharide of Escherichia coli in resistance to phagocytosis and serum killing. J Med Microbiol 24:363–370

    Article  CAS  PubMed  Google Scholar 

  21. Wills ED (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99:667–676

    CAS  PubMed  Google Scholar 

  22. Chanana V, Majumdar S, Rishi P (2007) Involvement of caspase-3, lipid peroxidation and TNF-α in causing apoptosis of macrophages by coordinately expressed Salmonella phenotype under stress conditions. Mol Immunol 44:1551–1558

    Article  CAS  PubMed  Google Scholar 

  23. Lowry OH, Rosenbrough NJ, Farr AL, Randell RJ (1951) Protein measurement with Folin’s phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  24. Chanana V, Majumdar S, Rishi P (2006) Tumor necrosis factor α mediated apoptosis in murine macrophages by Salmonella enterica serovar Typhi under oxidative stress. FEMS Immunol Med Microbiol 47:278–286

    Article  CAS  PubMed  Google Scholar 

  25. Luck H (1971) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic, New York, pp 885–894

    Google Scholar 

  26. Green LC, Wagner A, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  27. Christianson DW (1997) Structural chemistry and biology of manganese metalloenzymes. Prog Biophys Mol Biol 67:217–252

    Article  CAS  PubMed  Google Scholar 

  28. 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 70:6032–6042

    Article  CAS  PubMed  Google Scholar 

  29. Bearden SW, Perry RD (1999) The Yfe system of Yersinia pestis transports iron and manganese and is required for full virulence of plague. Mol Microbiol 32:403–414

    Article  CAS  PubMed  Google Scholar 

  30. Farr SB, Kogoma T (1991) Oxidative stress responses in Escherichia coli and Salmonella typhimurium. Microbiol Rev 55:561–585

    CAS  PubMed  Google Scholar 

  31. Tsolis RM, Baumler AJ, Heffron F (1995) Role of Salmonella typhimurium Mn-superoxide dismutase (SodA) in protection against early killing by J774 macrophages. Infect Immun 63:1739–1744

    CAS  PubMed  Google Scholar 

  32. Dougall WC, Nick HS (1991) Manganese superoxide dismutase: a hepatic acute phase protein regulated by interleukin-6 and glucocorticoids. Endocrinology 129:2376–2384

    Article  CAS  PubMed  Google Scholar 

  33. Fee JA (1991) Regulation of sod genes in Escherichia coli: relevance to superoxide dismutase function. Mol Microbiol 5:2599–2610

    Article  CAS  PubMed  Google Scholar 

  34. Hopkin KA, Papazian MA, Steinman HM (1992) Functional differences between manganese and iron superoxide dismutases in Escherichia coli K-12. J Biol Chem 267:24253–24258

    CAS  PubMed  Google Scholar 

  35. Hassan HM, Schrum LW (1994) Roles of manganese and iron in the regulation of the biosynthesis of manganese-superoxide dismutase in Escherichia coli. FEMS Microbiol Rev 14:315–323

    Article  CAS  PubMed  Google Scholar 

  36. Gerlach D, Reichardt W, Vettermann S (1998) Extracellular superoxide dismutase from Streptococcus pyogenes type 12 strain is manganese-dependent. FEMS Microbiol Lett 160:217–224

    Article  CAS  PubMed  Google Scholar 

  37. Law NA, Caudle MT, Pecoraro VL (1999) Manganese redox enzymes and model systems: properties, structures and reactivity. Adv Inorg Chem 46:305–440

    Article  Google Scholar 

  38. Yocum CF, Pecoraro V (1999) Recent advances in the understanding of the biological chemistry of manganese. Curr Opin Chem Biol 3:182–187

    Article  CAS  PubMed  Google Scholar 

  39. Whittaker JW (2000) Manganese superoxide dismutase. Met Ions Biol Syst 37:587–611

    CAS  PubMed  Google Scholar 

  40. Dunn KLR, Farrant JL, Langford PR, Kroll JS (2003) Bacterial [Cu, Zn]-cofactored superoxide dismutase protects opsonized, encapsulated Neisseria meningitidis from phagocytosis by human monocytes/macrophages. Infect Immun 71:1604–1607

    Article  CAS  PubMed  Google Scholar 

  41. Kehres DG, Maguire ME (2003) Emerging themes in manganese transport, biochemistry and pathogenesis in bacteria. FEMS Microbiol Rev 27:263–290

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, Basic Medical Sciences Block, Panjab University, Chandigarh, 160014, India

    Praveen Rishi, Natasha Jindal, Sushma Bharrhan & Ram Prakash Tiwari

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  1. Praveen Rishi
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  2. Natasha Jindal
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  3. Sushma Bharrhan
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  4. Ram Prakash Tiwari
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Correspondence to Praveen Rishi.

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Rishi, P., Jindal, N., Bharrhan, S. et al. Salmonella–Macrophage Interactions upon Manganese Supplementation. Biol Trace Elem Res 133, 110–119 (2010). https://doi.org/10.1007/s12011-009-8406-x

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  • DOI: https://doi.org/10.1007/s12011-009-8406-x

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