1887

Abstract

Metals are essential micronutrients for virtually all forms of life, but metal acquisition is a double-edged sword, because high concentrations of divalent cations can be toxic to the cell. Therefore, the genes involved in metal acquisition, storage and efflux are tightly regulated. The present study characterizes a nickel-responsive transcriptional regulator in the intracellular mammalian pathogen, Brucella abortus. Deletion of bab2_0432 (nikR) in B. abortus led to alterations in the nickel-responsive expression of the genes encoding the putative nickel importer NikABCDE and, moreover, NikR binds directly to a specific DNA sequence within the promoter region of nikA in a metal-dependent manner to control gene expression. While NikR is involved in controlling the expression of nikA, nikR is not required for the infection of macrophages or mice by B. abortus. Overall, this work characterizes the role of NikR in nickel-responsive gene expression, as well as the dispensability of nikR for Brucella virulence.

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2018-07-31
2019-12-05
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References

  1. Waldron KJ, Robinson NJ. How do bacterial cells ensure that metalloproteins get the correct metal?. Nat Rev Microbiol 2009;7:25–35 [CrossRef][PubMed]
    [Google Scholar]
  2. Roop RM. Metal acquisition and virulence in Brucella. Anim Health Res Rev 2012;13:10–20 [CrossRef][PubMed]
    [Google Scholar]
  3. Macomber L, Hausinger RP. Mechanisms of nickel toxicity in microorganisms. Metallomics 2011;3:1153–1162 [CrossRef][PubMed]
    [Google Scholar]
  4. Summers AO. Damage control: regulating defenses against toxic metals and metalloids. Curr Opin Microbiol 2009;12:138–144 [CrossRef][PubMed]
    [Google Scholar]
  5. von Bargen K, Gorvel JP, Salcedo SP. Internal affairs: investigating the Brucella intracellular lifestyle. FEMS Microbiol Rev 2012;36:533–562 [CrossRef][PubMed]
    [Google Scholar]
  6. Atluri VL, Xavier MN, de Jong MF, den Hartigh AB, Tsolis RM. Interactions of the human pathogenic Brucella species with their hosts. Annu Rev Microbiol 2011;65:523–541 [CrossRef][PubMed]
    [Google Scholar]
  7. de Figueiredo P, Ficht TA, Rice-Ficht A, Rossetti CA, Adams LG. Pathogenesis and immunobiology of brucellosis: review of Brucella-host interactions. Am J Pathol 2015;185:1505–1517 [CrossRef][PubMed]
    [Google Scholar]
  8. Roop RM, Gaines JM, Anderson ES, Caswell CC, Martin DW. Survival of the fittest: how Brucella strains adapt to their intracellular niche in the host. Med Microbiol Immunol 2009;198:221–238 [CrossRef][PubMed]
    [Google Scholar]
  9. Köhler S, Porte F, Jubier-Maurin V, Ouahrani-Bettache S, Teyssier J et al. The intramacrophagic environment of Brucella suis and bacterial response. Vet Microbiol 2002;90:299–309 [CrossRef][PubMed]
    [Google Scholar]
  10. Bandara AB, Contreras A, Contreras-Rodriguez A, Martins AM, Dobrean V et al. Brucella suis urease encoded by ure1 but not ure2 is necessary for intestinal infection of BALB/c mice. BMC Microbiol 2007;7:57 [CrossRef][PubMed]
    [Google Scholar]
  11. Sangari FJ, Cayón AM, Seoane A, García-Lobo JM. Brucella abortus ure2 region contains an acid-activated urea transporter and a nickel transport system. BMC Microbiol 2010;10:107 [CrossRef][PubMed]
    [Google Scholar]
  12. Sangari FJ, Seoane A, Rodríguez MC, Agüero J, García Lobo JM. Characterization of the urease operon of Brucella abortus and assessment of its role in virulence of the bacterium. Infect Immun 2007;75:774–780 [CrossRef][PubMed]
    [Google Scholar]
  13. Jubier-Maurin V, Rodrigue A, Ouahrani-Bettache S, Layssac M, Mandrand-Berthelot MA et al. Identification of the nik gene cluster of Brucella suis: regulation and contribution to urease activity. J Bacteriol 2001;183:426–434 [CrossRef][PubMed]
    [Google Scholar]
  14. Anderson ES, Paulley JT, Gaines JM, Valderas MW, Martin DW et al. The manganese transporter MntH is a critical virulence determinant for Brucella abortus 2308 in experimentally infected mice. Infect Immun 2009;77:3466–3474 [CrossRef][PubMed]
    [Google Scholar]
  15. Sheehan LM, Budnick JA, Roop RM, Caswell CC. Coordinated zinc homeostasis is essential for the wild-type virulence of Brucella abortus. J Bacteriol 2015;197:1582–1591 [CrossRef][PubMed]
    [Google Scholar]
  16. Paulley JT, Anderson ES, Roop RM. Brucella abortus requires the heme transporter BhuA for maintenance of chronic infection in BALB/c mice. Infect Immun 2007;75:5248–5254 [CrossRef][PubMed]
    [Google Scholar]
  17. Kim S, Watanabe K, Shirahata T, Watarai M. Zinc uptake system (znuA locus) of Brucella abortus is essential for intracellular survival and virulence in mice. J Vet Med Sci 2004;66:1059–1063 [CrossRef][PubMed]
    [Google Scholar]
  18. Lestrate P, Delrue RM, Danese I, Didembourg C, Taminiau B et al. Identification and characterization of in vivo attenuated mutants of Brucella melitensis. Mol Microbiol 2000;38:543–551 [CrossRef][PubMed]
    [Google Scholar]
  19. Lavigne JP, O'Callaghan D, Blanc-Potard AB. Requirement of MgtC for Brucella suis intramacrophage growth: a potential mechanism shared by Salmonella enterica and Mycobacterium tuberculosis for adaptation to a low-Mg2+ environment. Infect Immun 2005;73:3160–3163 [CrossRef][PubMed]
    [Google Scholar]
  20. Wattam AR, Foster JT, Mane SP, Beckstrom-Sternberg SM, Beckstrom-Sternberg JM et al. Comparative phylogenomics and evolution of the Brucellae reveal a path to virulence. J Bacteriol 2014;196:920–930 [CrossRef][PubMed]
    [Google Scholar]
  21. Bury-Moné S, Thiberge JM, Contreras M, Maitournam A, Labigne A et al. Responsiveness to acidity via metal ion regulators mediates virulence in the gastric pathogen Helicobacter pylori. Mol Microbiol 2004;53:623–638 [CrossRef][PubMed]
    [Google Scholar]
  22. De Pina K, Desjardin V, Mandrand-Berthelot MA, Giordano G, Wu LF. Isolation and characterization of the nikR gene encoding a nickel-responsive regulator in Escherichia coli. J Bacteriol 1999;181:670–674[PubMed]
    [Google Scholar]
  23. Budnick JA, Caswell CC. Nickel homeostasis in Brucella spp. In Roop Ii RM, Caswell CC. (editors) Metals and the Biology and Virulence of Brucella Cham: Springer International Publishing; 2017; pp.73–80
    [Google Scholar]
  24. Dosanjh NS, Michel SL. Microbial nickel metalloregulation: NikRs for nickel ions. Curr Opin Chem Biol 2006;10:123–130 [CrossRef][PubMed]
    [Google Scholar]
  25. Sheehan LM, Budnick JA, Blanchard C, Dunman PM, Caswell CC. A LysR-family transcriptional regulator required for virulence in Brucella abortus is highly conserved among the α-proteobacteria. Mol Microbiol 2015;98:318–328 [CrossRef][PubMed]
    [Google Scholar]
  26. Chivers PT, Sauer RT. Regulation of high affinity nickel uptake in bacteria. Ni2+-dependent interaction of NikR with wild-type and mutant operator sites. J Biol Chem 2000;275:19735–19741 [CrossRef][PubMed]
    [Google Scholar]
  27. Menscher EA, Caswell CC, Anderson ES, Roop RM. Mur regulates the gene encoding the manganese transporter MntH in Brucella abortus 2308. J Bacteriol 2012;194:561–566 [CrossRef][PubMed]
    [Google Scholar]
  28. van Vliet AH, Poppelaars SW, Davies BJ, Stoof J, Bereswill S et al. NikR mediates nickel-responsive transcriptional induction of urease expression in Helicobacter pylori. Infect Immun 2002;70:2846–2852 [CrossRef][PubMed]
    [Google Scholar]
  29. Caudill MT, Budnick JA, Sheehan LM, Lehman CR, Purwantini E et al. Proline utilization system is required for infection by the pathogenic α-proteobacterium Brucella abortus. Microbiology 2017;163:970–979 [CrossRef][PubMed]
    [Google Scholar]
  30. Sheehan LM, Budnick JA, Roop RM, Caswell CC. Coordinated zinc homeostasis is essential for the wild-type virulence of Brucella abortus. J Bacteriol 2015;197:1582–1591 [CrossRef][PubMed]
    [Google Scholar]
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