1887

Abstract

secretes two zinc-dependent metalloproteases, designated ZmpA and ZmpB. Previously, ZmpA and ZmpB have been shown to cleave several proteins important in host defence. In this study, the ability of ZmpA and ZmpB to digest and inactivate antimicrobial peptides involved in innate immunity was examined. ZmpB but not ZmpA cleaved -defensin-1. ZmpA but not ZmpB cleaved the cathelicidin LL-37. Both enzymes cleaved elafin and secretory leukocyte inhibitor, which are antimicrobial peptides as well as neutrophil elastase inhibitors. Both ZmpA and ZmpB cleaved protamine, a fish antimicrobial peptide, and a mutant was more sensitive to protamine killing than the parental strain. ZmpA or ZmpB cleavage of elafin inactivated its anti-protease activity. The effect of ZmpA and ZmpB on the neutrophil proteases elastase and cathepsin G was also examined but neither enzyme was active against these host proteases. These studies suggest that ZmpA and ZmpB may influence the resistance of to host antimicrobial peptides as well as alter the host protease/anti-protease balance in chronic respiratory infections.

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2009-09-01
2019-11-16
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References

  1. Alexander, B. D., Petzold, E. W., Reller, L. B., Palmer, S. M., Davis, R. D., Woods, C. W. & LiPuma, J. J. ( 2008; ). Survival after lung transplantation of cystic fibrosis patients infected with Burkholderia cepacia complex. Am J Transplant 8, 1025–1030.[CrossRef]
    [Google Scholar]
  2. Baird, R. M., Brown, H., Smith, A. W. & Watson, M. L. ( 1999; ). Burkholderia cepacia is resistant to the antimicrobial activity of airway epithelial cells. Immunopharmacology 44, 267–272.[CrossRef]
    [Google Scholar]
  3. Banemann, A., Deppisch, H. & Gross, R. ( 1998; ). The lipopolysaccharide of Bordetella bronchiseptica acts as a protective shield against antimicrobial peptides. Infect Immun 66, 5607–5612.
    [Google Scholar]
  4. Belaaouaj, A., McCarthy, R., Baumann, M., Gao, Z., Ley, T. J., Abraham, S. N. & Shapiro, S. D. ( 1998; ). Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med 4, 615–618.[CrossRef]
    [Google Scholar]
  5. Belaaouaj, A., Kim, K. S. & Shapiro, S. D. ( 2000; ). Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase. Science 289, 1185–1188.[CrossRef]
    [Google Scholar]
  6. Belas, R., Manos, J. & Suvanasuthi, R. ( 2004; ). Proteus mirabilis ZapA metalloprotease degrades a broad spectrum of substrates, including antimicrobial peptides. Infect Immun 72, 5159–5167.[CrossRef]
    [Google Scholar]
  7. Biddick, R., Spilker, T., Martin, A. & LiPuma, J. J. ( 2003; ). Evidence of transmission of Burkholderia cepacia, Burkholderia multivorans and Burkholderia dolosa among persons with cystic fibrosis. FEMS Microbiol Lett 228, 57–62.[CrossRef]
    [Google Scholar]
  8. Bressler, A. M., Kaye, K. S., LiPuma, J. J., Alexander, B. D., Moore, C. M., Reller, L. B. & Woods, C. W. ( 2007; ). Risk factors for Burkholderia cepacia complex bacteremia among intensive care unit patients without cystic fibrosis: a case-control study. Infect Control Hosp Epidemiol 28, 951–958.[CrossRef]
    [Google Scholar]
  9. Brogden, K. A. ( 2005; ). Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3, 238–250.[CrossRef]
    [Google Scholar]
  10. Brown, K. L. & Hancock, R. E. ( 2006; ). Cationic host defense (antimicrobial) peptides. Curr Opin Immunol 18, 24–30.[CrossRef]
    [Google Scholar]
  11. Burtnick, M. N. & Woods, D. E. ( 1999; ). Isolation of polymyxin B-susceptible mutants of Burkholderia pseudomallei and molecular characterization of genetic loci involved in polymyxin B resistance. Antimicrob Agents Chemother 43, 2648–2656.
    [Google Scholar]
  12. Chen, J. S., Witzmann, K. A., Spilker, T., Fink, R. J. & LiPuma, J. J. ( 2001; ). Endemicity and inter-city spread of Burkholderia cepacia genomovar III in cystic fibrosis. J Pediatr 139, 643–649.[CrossRef]
    [Google Scholar]
  13. Coenye, T. & LiPuma, J. J. ( 2003; ). Molecular epidemiology of Burkholderia species. Front Biosci 8, e55–e67.[CrossRef]
    [Google Scholar]
  14. Coenye, T., Vandamme, P., Govan, J. R. & LiPuma, J. J. ( 2001; ). Taxonomy and identification of the Burkholderia cepacia complex. J Clin Microbiol 39, 3427–3436.[CrossRef]
    [Google Scholar]
  15. Coenye, T., Vandamme, P., LiPuma, J. J., Govan, J. R. & Mahenthiralingam, E. ( 2003; ). Updated version of the Burkholderia cepacia complex experimental strain panel. J Clin Microbiol 41, 2797–2798.[CrossRef]
    [Google Scholar]
  16. Cooley, J., Takayama, T. K., Shapiro, S. D., Schechter, N. M. & Remold-O'Donnell, E. ( 2001; ). The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites. Biochemistry 40, 15762–15770.[CrossRef]
    [Google Scholar]
  17. Corbett, C. R., Burtnick, M. N., Kooi, C., Woods, D. E. & Sokol, P. A. ( 2003; ). An extracellular zinc metalloprotease gene of Burkholderia cepacia. Microbiology 149, 2263–2271.[CrossRef]
    [Google Scholar]
  18. Corey, M. & Farewell, V. ( 1996; ). Determinants of mortality from cystic fibrosis in Canada, 1970–1989. Am J Epidemiol 143, 1007–1017.[CrossRef]
    [Google Scholar]
  19. Cox, A. D. & Wilkinson, S. G. ( 1991; ). Ionizing groups in lipopolysaccharides of Pseudomonas cepacia in relation to antibiotic resistance. Mol Microbiol 5, 641–646.[CrossRef]
    [Google Scholar]
  20. Doumas, S., Kolokotronis, A. & Stefanopoulos, P. ( 2005; ). Anti-inflammatory and antimicrobial roles of secretory leukocyte protease inhibitor. Infect Immun 73, 1271–1274.[CrossRef]
    [Google Scholar]
  21. Drevinek, P., Holden, M. T., Ge, Z., Jones, A. M., Ketchell, I., Gill, R. T. & Mahenthiralingam, E. ( 2008; ). Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum. BMC Infect Dis 8, 121 [CrossRef]
    [Google Scholar]
  22. Gingues, S., Kooi, C., Visser, M. B., Subsin, B. & Sokol, P. A. ( 2005; ). Distribution and expression of the ZmpA metalloprotease in the Burkholderia cepacia complex. J Bacteriol 187, 8247–8255.[CrossRef]
    [Google Scholar]
  23. Govan, J. R., Brown, P. H., Maddison, J., Doherty, C. J., Nelson, J. W., Dodd, M., Greening, A. P. & Webb, A. K. ( 1993; ). Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 342, 15–19.[CrossRef]
    [Google Scholar]
  24. Govan, J. R., Brown, A. R. & Jones, A. M. ( 2007; ). Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection. Future Microbiol 2, 153–164.[CrossRef]
    [Google Scholar]
  25. Hansen, L. T., Austin, J. W. & Gill, T. A. ( 2001; ). Antibacterial effect of protamine in combination with EDTA and refrigeration. Int J Food Microbiol 66, 149–161.[CrossRef]
    [Google Scholar]
  26. Hartl, D., Latzin, P., Hordijk, P., Marcos, V., Rudolph, C., Woischnik, M., Krauss-Etschmann, S., Koller, B., Reinhardt, D. & other authors ( 2007; ). Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease. Nat Med 13, 1423–1430.[CrossRef]
    [Google Scholar]
  27. Hiemstra, P. S., Fernie-King, B. A., McMichael, J., Lachmann, P. J. & Sallenave, J. M. ( 2004; ). Antimicrobial peptides: mediators of innate immunity as templates for the development of novel anti-infective and immune therapeutics. Curr Pharm Des 10, 2891–2905.[CrossRef]
    [Google Scholar]
  28. Hwang, B. Y., Varadarajan, N., Li, H., Rodriguez, S., Iverson, B. L. & Georgiou, G. ( 2007; ). Substrate specificity of the Escherichia coli outer membrane protease OmpP. J Bacteriol 189, 522–530.[CrossRef]
    [Google Scholar]
  29. 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 Pediatr 104, 206–210.[CrossRef]
    [Google Scholar]
  30. Kooi, C., Corbett, C. R. & Sokol, P. A. ( 2005; ). Functional analysis of the Burkholderia cenocepacia ZmpA metalloprotease. J Bacteriol 187, 4421–4429.[CrossRef]
    [Google Scholar]
  31. Kooi, C., Subsin, B., Chen, R., Pohorelic, B. & Sokol, P. A. ( 2006; ). Burkholderia cenocepacia ZmpB is a broad-specificity zinc metalloprotease involved in virulence. Infect Immun 74, 4083–4093.[CrossRef]
    [Google Scholar]
  32. LiPuma, J. J. ( 2005; ). Update on the Burkholderia cepacia complex. Curr Opin Pulm Med 11, 528–533.[CrossRef]
    [Google Scholar]
  33. LiPuma, J. J., Dasen, S. E., Nielson, D. W., Stern, R. C. & Stull, T. L. ( 1990; ). Person-to-person transmission of Pseudomonas cepacia between patients with cystic fibrosis. Lancet 336, 1094–1096.[CrossRef]
    [Google Scholar]
  34. LiPuma, J. J., Spilker, T., Gill, L. H., Campbell, P. W., III, Liu, L. & Mahenthiralingam, E. ( 2001; ). Disproportionate distribution of Burkholderia cepacia complex species and transmissibility markers in cystic fibrosis. Am J Respir Crit Care Med 164, 92–96.[CrossRef]
    [Google Scholar]
  35. Loutet, S. A., Flannagan, R. S., Kooi, C., Sokol, P. A. & Valvano, M. A. ( 2006; ). A complete lipopolysaccharide inner core oligosaccharide is required for resistance of Burkholderia cenocepacia to antimicrobial peptides and bacterial survival in vivo. J Bacteriol 188, 2073–2080.[CrossRef]
    [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 Microbiol 38, 910–913.
    [Google Scholar]
  37. Mahenthiralingam, E., Urban, T. A. & Goldberg, J. B. ( 2005; ). The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 3, 144–156.[CrossRef]
    [Google Scholar]
  38. Mahenthiralingam, E., Baldwin, A. & Dowson, C. G. ( 2008; ). Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J Appl Microbiol 104, 1539–1551.[CrossRef]
    [Google Scholar]
  39. McDowell, A., Mahenthiralingam, E., Dunbar, K. E., Moore, J. E., Crowe, M. & Elborn, J. S. ( 2004; ). Epidemiology of Burkholderia cepacia complex species recovered from cystic fibrosis patients: issues related to patient segregation. J Med Microbiol 53, 663–668.[CrossRef]
    [Google Scholar]
  40. Mookherjee, N. & Hancock, R. E. ( 2007; ). Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol Life Sci 64, 922–933.[CrossRef]
    [Google Scholar]
  41. Morrison, G. M., Davidson, D. J., Kilanowski, F. M., Borthwick, D. W., Crook, K., Maxwell, A. I., Govan, J. R. & Dorin, J. R. ( 1998; ). Mouse beta defensin-1 is a functional homolog of human beta defensin-1. Mamm Genome 9, 453–457.[CrossRef]
    [Google Scholar]
  42. Murray, S., Charbeneau, J., Marshall, B. C. & LiPuma, J. J. ( 2008; ). Impact of Burkholderia infection on lung transplantation in cystic fibrosis. Am J Respir Crit Care Med 178, 363–371.[CrossRef]
    [Google Scholar]
  43. Nair, B. M., Cheung, K. J., Jr, Griffith, A. & Burns, J. L. ( 2004; ). Salicylate induces an antibiotic efflux pump in Burkholderia cepacia complex genomovar III (B. cenocepacia). J Clin Invest 113, 464–473.[CrossRef]
    [Google Scholar]
  44. Nair, B. M., Joachimiak, L. A., Chattopadhyay, S., Montano, I. & Burns, J. L. ( 2005; ). Conservation of a novel protein associated with an antibiotic efflux operon in Burkholderia cenocepacia. FEMS Microbiol Lett 245, 337–344.[CrossRef]
    [Google Scholar]
  45. Potempa, M., Potempa, J., Kantyka, T., Nguyen, K. A., Wawrzonek, K., Manandhar, S. P., Popadiak, K., Riesbeck, K., Eick, S. & Blom, A. M. ( 2009; ). Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3. PLoS Pathog 5, e1000316 [CrossRef]
    [Google Scholar]
  46. Rees, D. D. & Brain, J. D. ( 1995; ). Effects of cystic fibrosis airway secretions on rat lung: role of neutrophil elastase. Am J Physiol 269, L195–L202.
    [Google Scholar]
  47. Reeves, E. P., Lu, H., Jacobs, H. L., Messina, C. G., Bolsover, S., Gabella, G., Potma, E. O., Warley, A., Roes, J. & Segal, A. W. ( 2002; ). Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416, 291–297.[CrossRef]
    [Google Scholar]
  48. Reik, R., Spilker, T. & LiPuma, J. J. ( 2005; ). Distribution of Burkholderia cepacia complex species among isolates recovered from persons with or without cystic fibrosis. J Clin Microbiol 43, 2926–2928.[CrossRef]
    [Google Scholar]
  49. Rinderknecht, H., Geokas, M. C., Silverman, P. & Haverback, B. J. ( 1968; ). A new ultrasensitive method for the determination of proteolytic activity. Clin Chim Acta 21, 197–203.[CrossRef]
    [Google Scholar]
  50. Sahly, H., Schubert, S., Harder, J., Rautenberg, P., Ullmann, U., Schroder, J. & Podschun, R. ( 2003; ). Burkholderia is highly resistant to human beta-defensin 3. Antimicrob Agents Chemother 47, 1739–1741.[CrossRef]
    [Google Scholar]
  51. Sallenave, J. M. ( 2000; ). The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease. Respir Res 1, 87–92.[CrossRef]
    [Google Scholar]
  52. Schagger, H. & von Jagow, G. ( 1987; ). Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem 166, 368–379.[CrossRef]
    [Google Scholar]
  53. Schmidtchen, A., Frick, I. M., Andersson, E., Tapper, H. & Bjorck, L. ( 2002; ). Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 46, 157–168.[CrossRef]
    [Google Scholar]
  54. Shapiro, S. D. ( 2002; ). Neutrophil elastase: path clearer, pathogen killer, or just pathologic? Am J Respir Cell Mol Biol 26, 266–268.[CrossRef]
    [Google Scholar]
  55. Shimomura, H., Matsuura, M., Saito, S., Hirai, Y., Isshiki, Y. & Kawahara, K. ( 2003; ). Unusual interaction of a lipopolysaccharide isolated from Burkholderia cepacia with polymyxin B. Infect Immun 71, 5225–5230.[CrossRef]
    [Google Scholar]
  56. Sieprawska-Lupa, M., Mydel, P., Krawczyk, K., Wójcik, K., Puklo, M., Lupa, B., Suder, P., Silberring, J., Reed, M. & other authors ( 2004; ). Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother 48, 4673–4679.[CrossRef]
    [Google Scholar]
  57. Simpson, A. J., Maxwell, A. I., Govan, J. R., Haslett, C. & Sallenave, J. M. ( 1999; ). Elafin (elastase-specific inhibitor) has anti-microbial activity against gram-positive and gram-negative respiratory pathogens. FEBS Lett 452, 309–313.[CrossRef]
    [Google Scholar]
  58. Speert, D. P., Henry, D., Vandamme, P., Corey, M. & Mahenthiralingam, E. ( 2002; ). Epidemiology of Burkholderia cepacia complex in patients with cystic fibrosis, Canada. Emerg Infect Dis 8, 181–187.[CrossRef]
    [Google Scholar]
  59. Sponer, M., Nick, H. P. & Schnebli, H. P. ( 1991; ). Different susceptibility of elastase inhibitors to inactivation by proteinases from Staphylococcus aureus and Pseudomonas aeruginosa. Biol Chem Hoppe Seyler 372, 963–970.[CrossRef]
    [Google Scholar]
  60. Stumpe, S., Schmid, R., Stephens, D. L., Georgiou, G. & Bakker, E. P. ( 1998; ). Identification of OmpT as the protease that hydrolyzes the antimicrobial peptide protamine before it enters growing cells of Escherichia coli. J Bacteriol 180, 4002–4006.
    [Google Scholar]
  61. Thwaite, J. E., Hibbs, S., Titball, R. W. & Atkins, T. P. ( 2006; ). Proteolytic degradation of human antimicrobial peptide LL-37 by Bacillus anthracis may contribute to virulence. Antimicrob Agents Chemother 50, 2316–2322.[CrossRef]
    [Google Scholar]
  62. Vandamme, P., Holmes, B., Vancanneyt, M., Coenye, T., Hoste, B., Coopman, R., Revets, H., Lauwers, S., Gillis, M. & other authors ( 1997; ). Occurrence of multiple genomovars of Burkholderia cepacia in cystic fibrosis patients and proposal of Burkholderia multivorans sp. nov. Int J Syst Bacteriol 47, 1188–1200.[CrossRef]
    [Google Scholar]
  63. Vanlaere, E., LiPuma, J. J., Baldwin, A., Henry, D., De Brandt, E., Mahenthiralingam, E., Speert, D., Dowson, C. & Vandamme, P. ( 2008; ). Burkholderia latens sp. nov., Burkholderia diffusa sp. nov., Burkholderia arboris sp. nov., Burkholderia seminalis sp. nov. and Burkholderia metallica sp. nov., novel species within the Burkholderia cepacia complex. Int J Syst Evol Microbiol 58, 1580–1590.[CrossRef]
    [Google Scholar]
  64. Vanlaere, E., Baldwin, A., Gevers, D., Henry, D, De Brandt, E., LiPuma, J. J., Mahenthiralingam, E., Speert, D. P., Dowson, C. & Vandamme, P. ( 2009; ). Taxon K, a complex within the Burkholderia cepacia complex, comprises at least two novel species, Burkholderia contaminans sp. nov. and Burkholderia lata sp. nov. Int J Syst Evol Microbiol 59, 102–111.[CrossRef]
    [Google Scholar]
  65. Vial, L., Groleau, M. C., Dekimpe, V. & Deziel, E. ( 2007; ). Burkholderia diversity and versatility: an inventory of the extracellular products. J Microbiol Biotechnol 17, 1407–1429.
    [Google Scholar]
  66. Yount, N. Y. & Yeaman, M. R. ( 2005; ). Immunocontinuum: perspectives in antimicrobial peptide mechanisms of action and resistance. Protein Pept Lett 12, 49–67.[CrossRef]
    [Google Scholar]
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