Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Dec;64(12):4952–4959. doi: 10.1128/iai.64.12.4952-4959.1996

Burkholderia pseudomallei activates complement and is ingested but not killed by polymorphonuclear leukocytes.

A M Egan 1, D L Gordon 1
PMCID: PMC174474  PMID: 8945532

Abstract

The mechanism by which Burkholderia pseudomallei is resistant to lysis by human serum is unknown but may include interference with complement activation, effective opsonization, or complement-mediated lysis. We investigated the interaction of B. pseudomallei with complement in the presence and absence of specific antibody to determine potential mechanisms of serum resistance. We demonstrated rapid activation and consumption of complement by B. pseudomallei which, in the absence of specific antibody, occurred predominantly via the alternative pathway. Complement activation was associated with deposition of the opsonically active C3b and iC3b fragments on the bacterial surface. C5b-9, detected on the bacterial surface after opsonic periods of 1 to 60 min, was susceptible to elution by 1 M NaCl, indicating that resistance to complement-mediated lysis may result from deposition of the membrane attack complex in a nonmicrobicidal location. To define the role of opsonins, we investigated the ability of polymorphonuclear leukocytes (PMNL) to phagocytose B. pseudomallei. Phagocytosis of bacteria by PMNL, and the observed oxidative response, was significantly increased by opsonization of organisms with complement and/or specific antibody. Despite opsonophagocytosis by PMNL and the production of an oxidative response, no significant bacterial killing was observed.

Full Text

The Full Text of this article is available as a PDF (309.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashdown L. R. An improved screening technique for isolation of Pseudomonas pseudomallei from clinical specimens. Pathology. 1979 Apr;11(2):293–297. doi: 10.3109/00313027909061954. [DOI] [PubMed] [Google Scholar]
  2. Ashdown L. R., Guard R. W. The prevalence of human melioidosis in Northern Queensland. Am J Trop Med Hyg. 1984 May;33(3):474–478. doi: 10.4269/ajtmh.1984.33.474. [DOI] [PubMed] [Google Scholar]
  3. Ashdown L. R. Identification of Pseudomonas pseudomallei in the clinical laboratory. J Clin Pathol. 1979 May;32(5):500–504. doi: 10.1136/jcp.32.5.500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ashdown L. R., Johnson R. W., Koehler J. M., Cooney C. A. Enzyme-linked immunosorbent assay for the diagnosis of clinical and subclinical melioidosis. J Infect Dis. 1989 Aug;160(2):253–260. doi: 10.1093/infdis/160.2.253. [DOI] [PubMed] [Google Scholar]
  5. Chaowagul W., Suputtamongkol Y., Dance D. A., Rajchanuvong A., Pattara-arechachai J., White N. J. Relapse in melioidosis: incidence and risk factors. J Infect Dis. 1993 Nov;168(5):1181–1185. [PubMed] [Google Scholar]
  6. DANNENBERG A. M., Jr, SCOTT E. M. Melioidosis: pathogenesis and immunity in mice and hamsters. I. Studies with virulent strains of Malleomyces pseudomallei. J Exp Med. 1958 Jan 1;107(1):153–166. doi: 10.1084/jem.107.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dance D. A. Melioidosis: the tip of the iceberg? Clin Microbiol Rev. 1991 Jan;4(1):52–60. doi: 10.1128/cmr.4.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Desmarchelier P. M., Dance D. A., Chaowagul W., Suputtamongkol Y., White N. J., Pitt T. L. Relationships among Pseudomonas pseudomallei isolates from patients with recurrent melioidosis. J Clin Microbiol. 1993 Jun;31(6):1592–1596. doi: 10.1128/jcm.31.6.1592-1596.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drevets D. A., Campbell P. A. Roles of complement and complement receptor type 3 in phagocytosis of Listeria monocytogenes by inflammatory mouse peritoneal macrophages. Infect Immun. 1991 Aug;59(8):2645–2652. doi: 10.1128/iai.59.8.2645-2652.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fearon D. T. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med. 1980 Jul 1;152(1):20–30. doi: 10.1084/jem.152.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gordon D. L., Johnson G. M., Hostetter M. K. Ligand-receptor interactions in the phagocytosis of virulent Streptococcus pneumoniae by polymorphonuclear leukocytes. J Infect Dis. 1986 Oct;154(4):619–626. doi: 10.1093/infdis/154.4.619. [DOI] [PubMed] [Google Scholar]
  12. Gordon D. L., Rice J., Finlay-Jones J. J., McDonald P. J., Hostetter M. K. Analysis of C3 deposition and degradation on bacterial surfaces after opsonization. J Infect Dis. 1988 Apr;157(4):697–704. doi: 10.1093/infdis/157.4.697. [DOI] [PubMed] [Google Scholar]
  13. Hall B. F., Joiner K. A. Strategies of obligate intracellular parasites for evading host defences. Immunol Today. 1991 Mar;12(3):A22–A27. doi: 10.1016/S0167-5699(05)80007-6. [DOI] [PubMed] [Google Scholar]
  14. Heffernan E. J., Reed S., Hackett J., Fierer J., Roudier C., Guiney D. Mechanism of resistance to complement-mediated killing of bacteria encoded by the Salmonella typhimurium virulence plasmid gene rck. J Clin Invest. 1992 Sep;90(3):953–964. doi: 10.1172/JCI115972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ismail G., Razak N., Mohamed R., Embi N., Omar O. Resistance of Pseudomonas pseudomallei to normal human serum bactericidal action. Microbiol Immunol. 1988;32(7):645–652. doi: 10.1111/j.1348-0421.1988.tb01426.x. [DOI] [PubMed] [Google Scholar]
  16. Joiner K. A., Brown E. J., Frank M. M. Complement and bacteria: chemistry and biology in host defense. Annu Rev Immunol. 1984;2:461–491. doi: 10.1146/annurev.iy.02.040184.002333. [DOI] [PubMed] [Google Scholar]
  17. Joiner K. A. Complement evasion by bacteria and parasites. Annu Rev Microbiol. 1988;42:201–230. doi: 10.1146/annurev.mi.42.100188.001221. [DOI] [PubMed] [Google Scholar]
  18. Joiner K. A., Grossman N., Schmetz M., Leive L. C3 binds preferentially to long-chain lipopolysaccharide during alternative pathway activation by Salmonella montevideo. J Immunol. 1986 Jan;136(2):710–715. [PubMed] [Google Scholar]
  19. Joiner K. A., Hammer C. H., Brown E. J., Cole R. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. I. Terminal complement components are deposited and released from Salmonella minnesota S218 without causing bacterial death. J Exp Med. 1982 Mar 1;155(3):797–808. doi: 10.1084/jem.155.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Joiner K. A., Hammer C. H., Brown E. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of Salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane. J Exp Med. 1982 Mar 1;155(3):809–819. doi: 10.1084/jem.155.3.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jones A. L., Beveridge T. J., Woods D. E. Intracellular survival of Burkholderia pseudomallei. Infect Immun. 1996 Mar;64(3):782–790. doi: 10.1128/iai.64.3.782-790.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Law S. K., Lichtenberg N. A., Levine R. P. Evidence for an ester linkage between the labile binding site of C3b and receptive surfaces. J Immunol. 1979 Sep;123(3):1388–1394. [PubMed] [Google Scholar]
  23. Leelarasamee A., Bovornkitti S. Melioidosis: review and update. Rev Infect Dis. 1989 May-Jun;11(3):413–425. doi: 10.1093/clinids/11.3.413. [DOI] [PubMed] [Google Scholar]
  24. Mays E. E., Ricketts E. A. Melioidosis: recrudescence associated with bronchogenic carcinoma twenty-six years following initial geographic exposure. Chest. 1975 Aug;68(2):261–263. doi: 10.1378/chest.68.2.261. [DOI] [PubMed] [Google Scholar]
  25. Merino S., Albertí S., Tomás J. M. Aeromonas salmonicida resistance to complement-mediated killing. Infect Immun. 1994 Dec;62(12):5483–5490. doi: 10.1128/iai.62.12.5483-5490.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Moulder J. W. Comparative biology of intracellular parasitism. Microbiol Rev. 1985 Sep;49(3):298–337. doi: 10.1128/mr.49.3.298-337.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nelson B., Ruddy S. Enhancing role of IgG in lysis of rabbit erythrocytes by the alternative pathway of human complement. J Immunol. 1979 May;122(5):1994–1999. [PubMed] [Google Scholar]
  28. Payne N. R., Horwitz M. A. Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors. J Exp Med. 1987 Nov 1;166(5):1377–1389. doi: 10.1084/jem.166.5.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Piggott J. A., Hochholzer L. Human melioidosis. A histopathologic study of acute and chronic melioidosis. Arch Pathol. 1970 Aug;90(2):101–111. [PubMed] [Google Scholar]
  30. Pilz D., Vocke T., Heesemann J., Brade V. Mechanism of YadA-mediated serum resistance of Yersinia enterocolitica serotype O3. Infect Immun. 1992 Jan;60(1):189–195. doi: 10.1128/iai.60.1.189-195.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pramoonjago P., Kaneko M., Kinoshita T., Ohtsubo E., Takeda J., Hong K. S., Inagi R., Inoue K. Role of TraT protein, an anticomplementary protein produced in Escherichia coli by R100 factor, in serum resistance. J Immunol. 1992 Feb 1;148(3):827–836. [PubMed] [Google Scholar]
  32. Pruksachartvuthi S., Aswapokee N., Thankerngpol K. Survival of Pseudomonas pseudomallei in human phagocytes. J Med Microbiol. 1990 Feb;31(2):109–114. doi: 10.1099/00222615-31-2-109. [DOI] [PubMed] [Google Scholar]
  33. Schiller N. L., Joiner K. A. Interaction of complement with serum-sensitive and serum-resistant strains of Pseudomonas aeruginosa. Infect Immun. 1986 Dec;54(3):689–694. doi: 10.1128/iai.54.3.689-694.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schlesinger L. S., Bellinger-Kawahara C. G., Payne N. R., Horwitz M. A. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol. 1990 Apr 1;144(7):2771–2780. [PubMed] [Google Scholar]
  35. Schlesinger L. S., Horwitz M. A. Phagocytosis of leprosy bacilli is mediated by complement receptors CR1 and CR3 on human monocytes and complement component C3 in serum. J Clin Invest. 1990 Apr;85(4):1304–1314. doi: 10.1172/JCI114568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Verhoef J., Peterson P. K., Quie P. G. Kinetics of staphylococcal opsonization, attachment, ingestion and killing by human polymorphonuclear leukocytes: a quantitative assay using [3H]thymidine labeled bacteria. J Immunol Methods. 1977;14(3-4):303–311. doi: 10.1016/0022-1759(77)90141-7. [DOI] [PubMed] [Google Scholar]
  37. White N. J., Dance D. A., Chaowagul W., Wattanagoon Y., Wuthiekanun V., Pitakwatchara N. Halving of mortality of severe melioidosis by ceftazidime. Lancet. 1989 Sep 23;2(8665):697–701. doi: 10.1016/s0140-6736(89)90768-x. [DOI] [PubMed] [Google Scholar]
  38. Wong K. T., Puthucheary S. D., Vadivelu J. The histopathology of human melioidosis. Histopathology. 1995 Jan;26(1):51–55. doi: 10.1111/j.1365-2559.1995.tb00620.x. [DOI] [PubMed] [Google Scholar]
  39. Woods D. E., Jones A. L., Hill P. J. Interaction of insulin with Pseudomonas pseudomallei. Infect Immun. 1993 Oct;61(10):4045–4050. doi: 10.1128/iai.61.10.4045-4050.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES