1887

Abstract

Manganese has an important yet undefined role in the virulence of many bacterial pathogens. In this study we confirm that a null mutation in reduces intracellular manganese accumulation. An mutant was susceptible to killing by reactive oxygen species when grown under manganese-limited conditions. The mutant was defective in survival and growth in macrophages expressing functional Nramp1, but in macrophages deficient in Nramp the bacteria were able to survive and replicate. In , the mutant was attenuated. Taken together, these data suggest a role for manganese in during macrophage intracellular survival, protecting the bacteria from the antimicrobial products released during the respiratory burst.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.045807-0
2011-04-01
2019-09-21
Loading full text...

Full text loading...

/deliver/fulltext/micro/157/4/1115.html?itemId=/content/journal/micro/10.1099/mic.0.045807-0&mimeType=html&fmt=ahah

References

  1. Anderson, E. S., Paulley, J. T., Gaines, J. M., Valderas, M. W., Martin, D. W., Menscher, E., Brown, T. D., Burns, C. S. & Roop, R. M., II ( 2009; ). The manganese transporter MntH is a critical virulence determinant for Brucella abortus 2308 in experimentally infected mice. Infect Immun 77, 3466–3474.[CrossRef]
    [Google Scholar]
  2. Anjem, A., Varghese, S. & Imlay, J. A. ( 2009; ). Manganese import is a key element of the OxyR response to hydrogen peroxide in Escherichia coli. Mol Microbiol 72, 844–858.[CrossRef]
    [Google Scholar]
  3. Bearden, S. W. & Perry, R. D. ( 1999; ). The Yfe system of Yersinia pestis transports iron and manganese and is required for full virulence of plague. Mol Microbiol 32, 403–414.[CrossRef]
    [Google Scholar]
  4. Brown, I. N., Glynn, A. A. & Plant, J. ( 1982; ). Inbred mouse strain resistance to Mycobacterium lepraemurium follows the Ity/Lsh pattern. Immunology 47, 149–156.
    [Google Scholar]
  5. Brubaker, R. R. ( 1991; ). Factors promoting acute and chronic diseases caused by Yersiniae. Clin Microbiol Rev 4, 309–324.
    [Google Scholar]
  6. Carniel, E. ( 1999; ). The Yersinia high-pathogenicity island. Int Microbiol 2, 161–167.
    [Google Scholar]
  7. Carniel, E. ( 2002; ). Plasmids and pathogenicity islands of Yersinia. Curr Top Microbiol Immunol 264, 89–108.
    [Google Scholar]
  8. Cellier, M. F., Courville, P. & Campion, C. ( 2007; ). Nramp1 phagocyte intracellular metal withdrawal defense. Microbes Infect 9, 1662–1670.[CrossRef]
    [Google Scholar]
  9. Chain, P. S., Carniel, E., Larimer, F. W., Lamerdin, J., Stoutland, P. O., Regala, W. M., Georgescu, A. M., Vergez, L. M., Land, M. L. & other authors ( 2004; ). Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis. Proc Natl Acad Sci U S A 101, 13826–13831.[CrossRef]
    [Google Scholar]
  10. Champion, O. L., Cooper, I. A., James, S. L., Ford, D., Karlyshev, A., Wren, B. W., Duffield, M., Oyston, P. C. & Titball, R. W. ( 2009; ). Galleria mellonella as an alternative infection model for Yersinia pseudotuberculosis. Microbiology 155, 1516–1522.[CrossRef]
    [Google Scholar]
  11. Datsenko, K. A. & Wanner, B. L. ( 2000; ). One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97, 6640–6645.[CrossRef]
    [Google Scholar]
  12. Djaldetti, M., Salman, H., Bergman, M., Djaldetti, R. & Bessler, H. ( 2002; ). Phagocytosis – the mighty weapon of the silent warriors. Microsc Res Tech 57, 421–431.[CrossRef]
    [Google Scholar]
  13. Escolar, L., Pérez-Martín, J. & de Lorenzo, V. ( 1999; ). Opening the iron box: transcriptional metalloregulation by the Fur protein. J Bacteriol 181, 6223–6229.
    [Google Scholar]
  14. Forbes, J. R. & Gros, P. ( 2001; ). Divalent-metal transport by NRAMP proteins at the interface of host–pathogen interactions. Trends Microbiol 9, 397–403.[CrossRef]
    [Google Scholar]
  15. Forman, S., Paulley, J. T., Fetherston, J. D., Cheng, Y. Q. & Perry, R. D. ( 2010; ). Yersinia ironomics: comparison of iron transporters among Yersinia pestis biotypes and its nearest neighbor, Yersinia pseudotuberculosis. Biometals 23, 275–294.[CrossRef]
    [Google Scholar]
  16. Glynn, A. A., Bradley, D. J., Blackwell, J. M. & Plant, J. E. ( 1982; ). Genetics of resistance to infection. Lancet 320, 151.
    [Google Scholar]
  17. Govoni, G. & Gros, P. ( 1998; ). Macrophage NRAMP1 and its role in resistance to microbial infections. Inflamm Res 47, 277–284.[CrossRef]
    [Google Scholar]
  18. Grabenstein, J. P., Marceau, M., Pujol, C., Simonet, M. & Bliska, J. B. ( 2004; ). The response regulator PhoP of Yersinia pseudotuberculosis is important for replication in macrophages and for virulence. Infect Immun 72, 4973–4984.[CrossRef]
    [Google Scholar]
  19. Guzman, L. M., Belin, D., Carson, M. J. & Beckwith, J. ( 1995; ). Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol 177, 4121–4130.
    [Google Scholar]
  20. Hancock, G. E., Schaedler, R. W. & MacDonald, T. T. ( 1986; ). Yersinia enterocolitica infection in resistant and susceptible strains of mice. Infect Immun 53, 26–31.
    [Google Scholar]
  21. Hao, Z., Chen, S. & Wilson, D. B. ( 1999; ). Cloning, expression, and characterization of cadmium and manganese uptake genes from Lactobacillus plantarum. Appl Environ Microbiol 65, 4746–4752.
    [Google Scholar]
  22. Horsburgh, M. J., Wharton, S. J., Cox, A. G., Ingham, E., Peacock, S. & Foster, S. J. ( 2002; ). MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Mol Microbiol 44, 1269–1286.[CrossRef]
    [Google Scholar]
  23. Imlay, J. A. ( 2008; ). Cellular defenses against superoxide and hydrogen peroxide. Annu Rev Biochem 77, 755–776.[CrossRef]
    [Google Scholar]
  24. 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, 1237–1248.[CrossRef]
    [Google Scholar]
  25. Jakubovics, N. S. & Valentine, R. A. ( 2009; ). A new direction for manganese homeostasis in bacteria: identification of a novel efflux system in Streptococcus pneumoniae. Mol Microbiol 72, 1–4.[CrossRef]
    [Google Scholar]
  26. Johnston, J. W., Briles, D. E., Myers, L. E. & Hollingshead, S. K. ( 2006; ). Mn2+-dependent regulation of multiple genes in Streptococcus pneumoniae through PsaR and the resultant impact on virulence. Infect Immun 74, 1171–1180.[CrossRef]
    [Google Scholar]
  27. Kehres, D. G., Zaharik, M. L., Finlay, B. B. & Maguire, M. E. ( 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.[CrossRef]
    [Google Scholar]
  28. Kehres, D. G., Janakiraman, A., Slauch, J. M. & Maguire, M. E. ( 2002; ). SitABCD is the alkaline Mn2+ transporter of Salmonella enterica serovar Typhimurium. J Bacteriol 184, 3159–3166.[CrossRef]
    [Google Scholar]
  29. Maxson, M. E. & Darwin, A. J. ( 2004; ). Identification of inducers of the Yersinia enterocolitica phage shock protein system and comparison to the regulation of the RpoE and Cpx extracytoplasmic stress responses. J Bacteriol 186, 4199–4208.[CrossRef]
    [Google Scholar]
  30. Najdenski, H. M., Golkocheva, E. N., Vesselinova, A. M. & Rüssmann, H. ( 2004; ). Comparison of the course of infection of virulent Yersinia enterocolitica serotype O : 8 with an isogenic sodA mutant in the peroral rabbit model. Int J Med Microbiol 294, 383–393.[CrossRef]
    [Google Scholar]
  31. Outten, C. E. & O'Halloran, T. V. ( 2001; ). Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis. Science 292, 2488–2492.[CrossRef]
    [Google Scholar]
  32. Papp-Wallace, K. M. & Maguire, M. E. ( 2006; ). Manganese transport and the role of manganese in virulence. Annu Rev Microbiol 60, 187–209.[CrossRef]
    [Google Scholar]
  33. Patzer, S. I. & Hantke, K. ( 2001; ). Dual repression by Fe2+-Fur and Mn2+-MntR of the mntH gene, encoding an NRAMP-like Mn2+ transporter in Escherichia coli. J Bacteriol 183, 4806–4813.[CrossRef]
    [Google Scholar]
  34. Perry, R. D. ( 1993; ). Acquisition and storage of inorganic iron and hemin by the yersiniae. Trends Microbiol 1, 142–147.[CrossRef]
    [Google Scholar]
  35. Perry, R. D., Mier, I., Jr & Fetherston, J. D. ( 2007; ). Roles of the Yfe and Feo transporters of Yersinia pestis in iron uptake and intracellular growth. Biometals 20, 699–703.[CrossRef]
    [Google Scholar]
  36. Plant, J. & Glynn, A. A. ( 1976; ). Genetics of resistance to infection with Salmonella typhimurium in mice. J Infect Dis 133, 72–78.[CrossRef]
    [Google Scholar]
  37. Plant, J. E., Blackwell, J. M., O'Brien, A. D., Bradley, D. J. & Glynn, A. A. ( 1982; ). Are the Lsh and Ity disease resistance genes at one locus on mouse chromosome 1? Nature 297, 510–511.[CrossRef]
    [Google Scholar]
  38. Pujol, C. & Bliska, J. B. ( 2005; ). Turning Yersinia pathogenesis outside in: subversion of macrophage function by intracellular Yersiniae. Clin Immunol 114, 216–226.[CrossRef]
    [Google Scholar]
  39. Puri, S., Hohle, T. H. & O'Brian, M. R. ( 2010; ). Control of bacterial iron homeostasis by manganese. Proc Natl Acad Sci U S A 107, 10691–10695.[CrossRef]
    [Google Scholar]
  40. Que, Q. & Helmann, J. D. ( 2000; ). Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins. Mol Microbiol 35, 1454–1468.
    [Google Scholar]
  41. Reeve, I., Hummel, D., Nelson, N. & Voss, J. ( 2002; ). Overexpression, purification, and site-directed spin labeling of the Nramp metal transporter from Mycobacterium leprae. Proc Natl Acad Sci U S A 99, 8608–8613.[CrossRef]
    [Google Scholar]
  42. Rosch, J. W., Gao, G., Ridout, G., Wang, Y. D. & Tuomanen, E. I. ( 2009; ). Role of the manganese efflux system mntE for signalling and pathogenesis in Streptococcus pneumoniae. Mol Microbiol 72, 12–25.[CrossRef]
    [Google Scholar]
  43. Small, P. L., Isberg, R. R. & Falkow, S. ( 1987; ). Comparison of the ability of enteroinvasive Escherichia coli, Salmonella typhimurium, Yersinia pseudotuberculosis, and Yersinia enterocolitica to enter and replicate within HEp-2 cells. Infect Immun 55, 1674–1679.
    [Google Scholar]
  44. Taylor, L. A. & Rose, R. E. ( 1988; ). A correction in the nucleotide sequence of the Tn903 kanamycin resistance determinant in pUC4K. Nucleic Acids Res 16, 358.[CrossRef]
    [Google Scholar]
  45. Thomson, N. R., Howard, S., Wren, B. W., Holden, M. T., Crossman, L., Challis, G. L., Churcher, C., Mungall, K., Brooks, K. & other authors ( 2006; ). The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081. PLoS Genet 2, e206.[CrossRef]
    [Google Scholar]
  46. Turner, J. K., Xu, J. L. & Tapping, R. I. ( 2009; ). Substrains of 129 mice are resistant to Yersinia pestis KIM5: implications for IL-10 deficient mice. Infect Immun 77, 367–373.[CrossRef]
    [Google Scholar]
  47. Verneuil, N., Mazé, A., Sanguinetti, M., Laplace, J. M., Benachour, A., Auffray, Y., Giard, J. C. & Hartke, A. ( 2006; ). Implication of (Mn)superoxide dismutase of Enterococcus faecalis in oxidative stress responses and survival inside macrophages. Microbiology 152, 2579–2589.[CrossRef]
    [Google Scholar]
  48. Vidal, S., Tremblay, M. L., Govoni, G., Gauthier, S., Sebastiani, G., Malo, D., Skamene, E., Olivier, M., Jothy, S. & Gros, P. ( 1995; ). The ity/lsh/bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J Exp Med 182, 655–666.[CrossRef]
    [Google Scholar]
  49. White, J. K., Stewart, A., Popoff, J. F., Wilson, S. & Blackwell, J. M. ( 2004; ). Incomplete glycosylation and defective intracellular targeting of mutant solute carrier family 11 member 1 (Slc11a1). Biochem J 382, 811–819.[CrossRef]
    [Google Scholar]
  50. Zaharik, M. L. & Finlay, B. B. ( 2004; ). Mn2+ and bacterial pathogenesis. Front Biosci 9, 1035–1042.[CrossRef]
    [Google Scholar]
  51. Zwilling, B. S. & Hilburger, M. E. ( 1994; ). Macrophage resistance genes: bcg/ity/lsh. Immunol Ser 60, 233–245.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.045807-0
Loading
/content/journal/micro/10.1099/mic.0.045807-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error