1887

Abstract

causes chronic lung infections in patients suffering from cystic fibrosis and chronic granulomatous disease. We have previously shown that survives intracellularly in macrophages within a membrane vacuole (BcCV) that delays acidification. Here, we report that after macrophage infection with live there is a ∼6 h delay in the association of NADPH oxidase with BcCVs, while heat-inactivated bacteria are normally trafficked into NADPH oxidase-positive vacuoles. BcCVs in macrophages treated with a functional inhibitor of the cystic fibrosis transmembrane conductance regulator exhibited a further delay in the assembly of the NADPH oxidase complex at the BcCV membrane, but the inhibitor did not affect NADPH oxidase complex assembly onto vacuoles containing heat-inactivated or live . Macrophages produced less superoxide following infection as compared to heat-inactivated and controls. Reduced superoxide production was associated with delayed deposition of cerium perhydroxide precipitates around BcCVs of macrophages infected with live , as visualized by transmission electron microscopy. Together, our results demonstrate that intracellular resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane. This phenomenon may contribute to preventing the efficient clearance of this opportunistic pathogen from the infected airways of susceptible patients.

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2009-04-01
2020-04-01
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References

  1. Allen L. A., Beecher B. R., Lynch J. T., Rohner O. V., Wittine L. M.. 2005; Helicobacter pylori disrupts NADPH oxidase targeting in human neutrophils to induce extracellular superoxide release. J Immunol174:3658–3667
    [Google Scholar]
  2. Aubert D. F., Flannagan R. S., Valvano M. A.. 2008; A novel sensor kinase-response regulator hybrid controls biofilm formation and virulence in Burkholderia cenocepacia . Infect Immun76:1979–1991
    [Google Scholar]
  3. Bokoch G. M., Diebold B. A.. 2002; Current molecular models for NADPH oxidase regulation by Rac GTPase. Blood100:2692–2696
    [Google Scholar]
  4. Burns J. L., Jonas M., Chi E. Y., Clark D. K., Berger A., Griffith A.. 1996; Invasion of respiratory epithelial cells by Burkholderia ( Pseudomonas ) cepacia . Infect Immun64:4054–4059
    [Google Scholar]
  5. Bylund J., Campsall P. A., Ma R. C., Conway B. A., Speert D. P.. 2005; Burkholderia cenocepacia induces neutrophil necrosis in chronic granulomatous disease. J Immunol174:3562–3569
    [Google Scholar]
  6. Carlyon J. A., Fikrig E.. 2006; Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum . Curr Opin Hematol13:28–33
    [Google Scholar]
  7. Chen J., He R., Minshall R. D., Dinauer M. C., Ye R. D.. 2007; Characterization of a mutation in the Phox homology domain of the NADPH oxidase component p40 phox identifies a mechanism for negative regulation of superoxide production. J Biol Chem282:30273–30284
    [Google Scholar]
  8. Cheng S. H., Gregory R. J., Marshall J., Paul S., Souza D. W., White G. A., O'Riordan C. R., Smith A. E.. 1990; Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell63:827–834
    [Google Scholar]
  9. Chiu C. H., Ostry A., Speert D. P.. 2001; Invasion of murine respiratory epithelial cells in vivo by Burkholderia cepacia . J Med Microbiol50:594–601
    [Google Scholar]
  10. Coenye T., Vandamme P.. 2003; Diversity and significance of Burkholderia species occupying diverse ecological niches. Environ Microbiol5:719–729
    [Google Scholar]
  11. De Leo F. R., Ulman K. V., Davis A. R., Jutila K. L., Quinn M. T.. 1996; Assembly of the human neutrophil NADPH oxidase involves binding of p67 phox and flavocytochrome b to a common functional domain in p47 phox . J Biol Chem271:17013–17020
    [Google Scholar]
  12. Di A., Brown M. E., Deriy L. V., Li C., Szeto F. L., Chen Y., Huang P., Tong J., Naren A. P.. other authors 2006; CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol8:933–944
    [Google Scholar]
  13. Dinauer M. C., Orkin S. H.. 1992; Chronic granulomatous disease. Annu Rev Med43:117–124
    [Google Scholar]
  14. Fang F. C.. 2004; Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol2:820–832
    [Google Scholar]
  15. Gallois A., Klein J. R., Allen L. A., Jones B. D., Nauseef W. M.. 2001; Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane. J Immunol166:5741–5748
    [Google Scholar]
  16. Guide S. V., Stock F., Gill V. J., Anderson V. L., Malech H. L., Gallin J. I., Holland S. M.. 2003; Reinfection, rather than persistent infection, in patients with chronic granulomatous disease. J Infect Dis187:845–853
    [Google Scholar]
  17. Haggie P. M., Verkman A. S.. 2007; Cystic fibrosis transmembrane conductance regulator-independent phagosomal acidification in macrophages. J Biol Chem282:31422–31428
    [Google Scholar]
  18. Han C. H., Freeman J. L., Lee T., Motalebi S. A., Lambeth J. D.. 1998; Regulation of the neutrophil respiratory burst oxidase. Identification of an activation domain in p67 phox . J Biol Chem273:16663–16668
    [Google Scholar]
  19. Heyworth P. G., Curnutte J. T., Nauseef W. M., Volpp B. D., Pearson D. W., Rosen H., Clark R. A.. 1991; Neutrophil nicotinamide adenine dinucleotide phosphate oxidase assembly. Translocation of p47- phox and p67- phox requires interaction between p47- phox and cytochrome b 558. J Clin Invest87:352–356
    [Google Scholar]
  20. Holt P. G., Strickland D. H., Wikstrom M. E., Jahnsen F. L.. 2008; Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol8:142–152
    [Google Scholar]
  21. Isles A., Maclusky I., Corey M., Gold R., Prober C., Fleming P., Levison H.. 1984; Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J Pediatr104:206–210
    [Google Scholar]
  22. Keig P. M., Ingham E., Vandamme P. A., Kerr K. G.. 2002; Differential invasion of respiratory epithelial cells by members of the Burkholderia cepacia complex. Clin Microbiol Infect8:47–49
    [Google Scholar]
  23. Keith K. E., Valvano M. A.. 2007; Characterization of SodC, a periplasmic superoxide dismutase from Burkholderia cenocepacia . Infect Immun75:2451–2460
    [Google Scholar]
  24. Keith K. E., Killip L., He P., Moran G. H., Valvano M. A.. 2007; Burkholderia cenocepacia C5424 produces a pigment with antioxidant properties using a homogentisate intermediate. J Bacteriol189:9057–9065
    [Google Scholar]
  25. Kuribayashi F., Nunoi H., Wakamatsu K., Tsunawaki S., Sato K., Ito T., Sumimoto H.. 2002; The adaptor protein p40 phox as a positive regulator of the superoxide-producing phagocyte oxidase. EMBO J21:6312–6320
    [Google Scholar]
  26. Lamothe J., Valvano M. A.. 2008; Burkholderia cenocepacia -induced delay of acidification and phagolysosomal fusion in cystic fibrosis transmembrane conductance regulator (CFTR)-defective macrophages. Microbiology154:3825–3834
    [Google Scholar]
  27. Lamothe J., Thyssen S., Valvano M. A.. 2004; Burkholderia cepacia complex isolates survive intracellularly without replication within acidic vacuoles of Acanthamoeba polyphaga . Cell Microbiol6:1127–1138
    [Google Scholar]
  28. Lamothe J., Huynh K. K., Grinstein S., Valvano M. A.. 2007; Intracellular survival of Burkholderia cenocepacia in macrophages is associated with a delay in the maturation of bacteria-containing vacuoles. Cell Microbiol9:40–53
    [Google Scholar]
  29. Landers P., Kerr K. G., Rowbotham T. J., Tipper J. L., Keig P. M., Ingham E., Denton M.. 2000; Survival and growth of Burkholderia cepacia within the free-living amoeba Acanthamoeba polyphaga . Eur J Clin Microbiol Infect Dis19:121–123
    [Google Scholar]
  30. Lefebre M. D., Valvano M. A.. 2002; Construction and evaluation of plasmid vectors optimized for constitutive and regulated gene expression in Burkholderia cepacia complex isolates. Appl Environ Microbiol68:5956–5964
    [Google Scholar]
  31. Lipuma J. J.. 2005; Update on the Burkholderia cepacia complex. Curr Opin Pulm Med11:528–533
    [Google Scholar]
  32. Lodge R., Descoteaux A.. 2006; Phagocytosis of Leishmania donovani amastigotes is Rac1 dependent and occurs in the absence of NADPH oxidase activation. Eur J Immunol36:2735–2744
    [Google Scholar]
  33. Lodge R., Diallo T. O., Descoteaux A.. 2006; Leishmania donovani lipophosphoglycan blocks NADPH oxidase assembly at the phagosome membrane. Cell Microbiol8:1922–1931
    [Google Scholar]
  34. Ma T., Thiagarajah J. R., Yang H., Sonawane N. D., Folli C., Galietta L. J., Verkman A. S.. 2002; Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J Clin Invest110:1651–1658
    [Google Scholar]
  35. Macdonald K. L., Speert D. P.. 2008; Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cells. Cell Microbiol10:2138–2149
    [Google Scholar]
  36. Mahenthiralingam E., Coenye T., Chung J. W., Speert D. P., Govan J. R., Taylor P., Vandamme P.. 2000; Diagnostically and experimentally useful panel of strains from the Burkholderia cepacia complex. J Clin Microbiol38:910–913
    [Google Scholar]
  37. Mahenthiralingam E., Urban T. A., Goldberg J. B.. 2005; The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol3:144–156
    [Google Scholar]
  38. Mahenthiralingam E., Baldwin A., Dowson C. G.. 2008; Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J Appl Microbiol104:1539–1551
    [Google Scholar]
  39. Maloney K. E., Valvano M. A.. 2006; The mgtC gene of Burkholderia cenocepacia is required for growth under magnesium limitation conditions and intracellular survival in macrophages. Infect Immun74:5477–5486
    [Google Scholar]
  40. Marolda C. L., Hauröder B., John M. A., Michel R., Valvano M. A.. 1999; Intracellular survival and saprophytic growth of isolates from the Burkholderia cepacia complex in free-living amoebae. Microbiology145:1509–1517
    [Google Scholar]
  41. Martin D. W., Mohr C. D.. 2000; Invasion and intracellular survival of Burkholderia cepacia . Infect Immun68:24–29
    [Google Scholar]
  42. Minakami R., Sumimotoa H.. 2006; Phagocytosis-coupled activation of the superoxide-producing phagocyte oxidase, a member of the NADPH oxidase (Nox) family. Int J Hematol84:193–198
    [Google Scholar]
  43. Mott J., Rikihisa Y., Tsunawaki S.. 2002; Effects of Anaplasma phagocytophila on NADPH oxidase components in human neutrophils and HL-60 cells. Infect Immun70:1359–1366
    [Google Scholar]
  44. Nakashima T., Iwashita T., Fujita T., Sato E., Niwano Y., Kohno M., Kuwahara S., Harada N., Takeshita S., Oda T.. 2008; A prodigiosin analogue inactivates NADPH oxidase in macrophage cells by inhibiting assembly of p47 phox and Rac. J Biochem143:107–115
    [Google Scholar]
  45. Nauseef W. M., Volpp B. D., McCormick S., Leidal K. G., Clark R. A.. 1991; Assembly of the neutrophil respiratory burst oxidase. Protein kinase C promotes cytoskeletal and membrane association of cytosolic oxidase components. J Biol Chem266:5911–5917
    [Google Scholar]
  46. O'Donnell B. V., Tew D. G., Jones O. T., England P. J.. 1993; Studies on the inhibitory mechanism of iodonium compounds with special reference to neutrophil NADPH oxidase. Biochem J290:41–49
    [Google Scholar]
  47. Perez A., Issler A. C., Cotton C. U., Kelley T. J., Verkman A. S., Davis P. B.. 2007; CFTR inhibition mimics the cystic fibrosis inflammatory profile. Am J Physiol Lung Cell Mol Physiol292:L383–L395
    [Google Scholar]
  48. Rook G. A., Steele J., Umar S., Dockrell H. M.. 1985; A simple method for the solubilisation of reduced NBT, and its use as a colorimetric assay for activation of human macrophages by gamma-interferon. J Immunol Methods82:161–167
    [Google Scholar]
  49. Saini L. S., Galsworthy S. B., John M. A., Valvano M. A.. 1999; Intracellular survival of Burkholderia cepacia complex isolates in the presence of macrophage cell activation. Microbiology145:3465–3475
    [Google Scholar]
  50. Sajjan U. S., Yang J. H., Hershenson M. B., LiPuma J. J.. 2006; Intracellular trafficking and replication of Burkholderia cenocepacia in human cystic fibrosis airway epithelial cells. Cell Microbiol8:1456–1466
    [Google Scholar]
  51. Sajjan S. U., Carmody L. A., Gonzalez C. F., LiPuma J. J.. 2008; A type IV secretion system contributes to intracellular survival and replication of Burkholderia cenocepacia . Infect Immun76:5447–5455
    [Google Scholar]
  52. Saldías M. S., Lamothe J., Wu R., Valvano M. A.. 2008; Burkholderia cenocepacia requires the RpoN sigma factor for biofilm formation and intracellular trafficking within macrophages. Infect Immun76:1059–1067
    [Google Scholar]
  53. Segal A. W.. 2005; How neutrophils kill microbes. Annu Rev Immunol23:197–223
    [Google Scholar]
  54. Takeya R., Sumimoto H.. 2003; Molecular mechanism for activation of superoxide-producing NADPH oxidases. Mol Cells16:271–277
    [Google Scholar]
  55. Telek G., Scoazec J. Y., Chariot J., Ducroc R., Feldmann G., Rozé C.. 1999; Cerium-based histochemical demonstration of oxidative stress in taurocholate-induced acute pancreatitis in rats. A confocal laser scanning microscopic study. J Histochem Cytochem47:1201–1212
    [Google Scholar]
  56. Ueyama T., Tatsuno T., Kawasaki T., Tsujibe S., Shirai Y., Sumimoto H., Leto T. L., Saito N.. 2007; A regulated adaptor function of p40 phox : distinct p67 phox membrane targeting by p40 phox and by p47 phox . Mol Biol Cell18:441–454
    [Google Scholar]
  57. Valvano M. A.. 2006; Infections by Burkholderia species: the psycho-dramatic life of an opportunistic pathogen. Future Microbiol1:145–149
    [Google Scholar]
  58. Valvano M. A., Keith K. E., Cardona S. T.. 2005; Survival and persistence of opportunistic Burkholderia species in host cells. Curr Opin Microbiol8:99–105
    [Google Scholar]
  59. Vazquez-Torres A., Fang F. C.. 2001; Oxygen-dependent anti- Salmonella activity of macrophages. Trends Microbiol9:29–33
    [Google Scholar]
  60. Vazquez-Torres A., Xu Y., Jones-Carson J., Holden D. W., Lucia S. M., Dinauer M. C., Mastroeni P., Fang F. C.. 2000; Salmonella pathogenicity island 2-dependent evasion of the phagocyte NADPH oxidase. Science287:1655–1658
    [Google Scholar]
  61. Vignais P. V.. 2002; The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci59:1428–1459
    [Google Scholar]
  62. Waterman S. R., Holden D. W.. 2003; Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system. Cell Microbiol5:501–511
    [Google Scholar]
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