Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei


Burkholderia pseudomallei is a potential bioterror agent and the causative agent of melioidosis, a severe disease that is endemic in areas of Southeast Asia and Northern Australia. Infection is often associated with bacterial dissemination to distant sites, and there are many possible disease manifestations, with melioidosis septic shock being the most severe. Eradication of the organism following infection is difficult, with a slow fever-clearance time, the need for prolonged antibiotic therapy and a high rate of relapse if therapy is not completed. Mortality from melioidosis septic shock remains high despite appropriate antimicrobial therapy. Prevention of disease and a reduction in mortality and the rate of relapse are priority areas for future research efforts. Studying how the disease is acquired and the host–pathogen interactions involved will underpin these efforts; this review presents an overview of current knowledge in these areas, highlighting key topics for evaluation.

Key Points

  • Melioidosis is caused by the aerobic, Gram-negative soil-dwelling bacillus Burkholderia pseudomallei and is an important cause of severe sepsis in Southeast Asia and Northern Australia. The high associated mortality rate, wide availability in the environment in endemic areas, intrinsic resistance to many antibiotics and the potential for aerosol spread has made this organism a potential bioterror agent.

  • The genome of B. pseudomallei consists of a large chromosome (4.07 Mb) carrying genes mainly associated with cell growth and metabolism, and a smaller chromosome (3.17 Mb) which has a greater proportion of genes encoding accessory functions such as adaptation and survival in different environments. Approximately 6% of the genome is made up of genomic islands that have probably been acquired by horizontal gene transfer.

  • Factors associated with disease acquisition in endemic regions include adverse weather conditions, the route and size of the inoculum and the integrity of the host immune system. The geographical incidence of B. pseudomallei and typical clinical features of the disease are reviewed.

  • No single B. pseudomallei determinant has been shown to have a role in virulence during human disease, persistence or latency. However, putative virulence factors include quorum sensing, a type III secretion system, capsular polysaccharide and, with less conclusive evidence, lipopolysaccharide and flagella.

  • B. pseudomallei is an intracellular pathogen that multiplies within macrophages. Recent data have shed light on the mechanisms that this bacterium uses to adapt to, and exploit, the intracellular environment. IFN-γ and TNF-α have an important role in early resistance against B. pseudomallei infection. Although more is becoming known about the pathogenesis of this bacterium in disease, the host–pathogen interactions are still ill-defined.

  • Potential new therapies that warrant further clinical evaluation include granulocyte colony-stimulating factor and CpG (bacterial DNA). Development of an effective human melioidosis vaccine is a research priority.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Selected clinical features of melioidosis, the 'great mimicker'.
Figure 2: Clinical isolates of Burkholderia pseudomallei.
Figure 3: The phylogeny of the Burkholderia genus.
Figure 4: The intracellular lifestyle of Burkholderia pseudomallei.
Figure 5: Host–pathogen interactions in Burkholderia pseudomallei infection: bacterial virulence meets innate immunity.


  1. 1

    Dance, D. A. Melioidosis: the tip of the iceberg? Clin. Microbiol. Rev. 4, 52–60 (1991).

  2. 2

    White, N. J. Melioidosis. Lancet 361, 1715–1722 (2003).

  3. 3

    Ngauy, V., Lemeshev, Y., Sadkowski, L. & Crawford, G. Cutaneous melioidosis in a man who was taken as a prisoner of war by the Japanese during World War II. J. Clin. Microbiol. 43, 970–972 (2005).

  4. 4

    Cheng, A. C. & Currie, B. J. Melioidosis: epidemiology, pathophysiology, and management. Clin. Microbiol. Rev. 18, 383–416 (2005).

  5. 5

    Cheng, A. C. et al. Melioidosis in northern Australia, 2001–02. Commun. Dis. Intell. 27, 272–277 (2003).

  6. 6

    Brett, P. J., DeShazer, D. & Woods, D. E. Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei-like species. Int. J. Syst. Bacteriol. 48, 317–320 (1998). First description of B. thailandensis.

  7. 7

    Holden, M. T. et al. Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei. Proc. Natl Acad. Sci. USA 101, 14240–14245 (2004). Provided the complete genome sequence of B. pseudomallei and a description of the pathogenicity islands.

  8. 8

    Nierman, W. C. et al. Structural flexibility in the Burkholderia mallei genome. Proc. Natl Acad. Sci. USA 101, 14246–14251 (2004).

  9. 9

    Godoy, D. et al. Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei. J. Clin. Microbiol. 41, 2068–20679 (2003). Description of the development of MLST for B. pseudomallei.

  10. 10

    Ong, C. et al. Patterns of large-scale genomic variation in virulent and avirulent Burkholderia species. Genome Res. 14, 2295–2307 (2004).

  11. 11

    Reckseidler, S. L., DeShazer, D., Sokol, P. A. & Woods, D. E. Detection of bacterial virulence genes by subtractive hybridization: identification of capsular polysaccharide of Burkholderia pseudomallei as a major virulence determinant. Infect. Immun. 69, 34–44 (2001).

  12. 12

    Brown, N. F. & Beacham, I. R. Cloning and analysis of genomic differences unique to Burkholderia pseudomallei by comparison with B. thailandensis. J. Med. Microbiol. 49, 993–1001 (2000).

  13. 13

    Vuddhakul, V. et al. Epidemiology of Burkholderia pseudomallei in Thailand. Am. J. Trop. Med. Hyg. 60, 458–461 (1999).

  14. 14

    Parry, C. M. et al. Melioidosis in Southern Vietnam: clinical surveillance and environmental sampling. Clin. Infect. Dis. 29, 1323–1326 (1999).

  15. 15

    Wuthiekanun, V. et al. Detection of Burkholderia pseudomallei in soil within the Lao People's Democratic Republic. J. Clin. Microbiol. 43, 923–924 (2005).

  16. 16

    Currie, B. J. & Jacups, S. P. Intensity of rainfall and severity of melioidosis, Australia. Emerg. Infect. Dis. 9, 1538–1542 (2003). Showed that heavy rains and winds can cause a shift towards inhalation of B. pseudomallei.

  17. 17

    Chierakul, W. et al. Melioidosis in 6 tsunami survivors in Southern Thailand. Clin. Infect. Dis. 41, 982–990 (2005).

  18. 18

    Kanaphun, P. et al. Serology and carriage of Pseudomonas pseudomallei: a prospective study in 1000 hospitalized children in northeast Thailand. J. Infect. Dis. 167, 230–233 (1993).

  19. 19

    Currie, B. J. et al. The epidemiology of melioidosis in Australia and Papua New Guinea. Acta Trop. 74, 121–127 (2000).

  20. 20

    Maharjan, B. et al. Recurrent melioidosis in patients in northeast Thailand is frequently due to reinfection rather than relapse. J. Clin. Microbiol. 43, 6032–6034 (2005).

  21. 21

    Lazdunski, A. M., Ventre, I. & Sturgis, J. N. Regulatory circuits and communication in Gram-negative bacteria. Nature Rev. Microbiol. 2, 581–592 (2004).

  22. 22

    Ulrich, R. L. et al. Role of quorum sensing in the pathogenicity of Burkholderia pseudomallei. J. Med. Microbiol. 53, 1053–1064 (2004).

  23. 23

    Valade, E. et al. The PmlI-PmlR quorum-sensing system in Burkholderia pseudomallei plays a key role in virulence and modulates production of the MprA protease. J. Bacteriol. 186, 2288–2294 (2004).

  24. 24

    Song, Y. et al. The BpsIR quorum-sensing system of Burkholderia pseudomallei. J. Bacteriol. 187, 785–790 (2005).

  25. 25

    Chan, Y. Y. & Chua, K. L. The Burkholderia pseudomallei BpeAB-OprB efflux pump: expression and impact on quorum sensing and virulence. J. Bacteriol. 187, 4707–4719 (2005).

  26. 26

    Rainbow, L., Hart, C. A. & Winstanley, C. Distribution of type III secretion gene clusters in Burkholderia pseudomallei, B. thailandensis and B. mallei. J. Med. Microbiol. 51, 374–384 (2002).

  27. 27

    Warawa, J. & Woods, D. E. Type III secretion system cluster 3 is required for maximal virulence of Burkholderia pseudomallei in a hamster infection model. FEMS Microbiol. Lett. 242, 101–108 (2005).

  28. 28

    Attree, O. & Attree, I. A second type III secretion system in Burkholderia pseudomallei: who is the real culprit? Microbiology 147, 3197–3199 (2001).

  29. 29

    Stevens, M. P. et al. An Inv/Mxi-Spa-like type III protein secretion system in Burkholderia pseudomallei modulates intracellular behaviour of the pathogen. Mol. Microbiol. 46, 649–659 (2002).

  30. 30

    Cornelis, G. R. & Van Gijsegem, F. Assembly and function of type III secretory systems. Annu. Rev. Microbiol. 54, 735–774 (2000).

  31. 31

    Stevens, M. P. et al. A Burkholderia pseudomallei type III secreted protein, BopE, facilitates bacterial invasion of epithelial cells and exhibits guanine nucleotide exchange factor activity. J. Bacteriol. 185, 4992–4996 (2003).

  32. 32

    Stevens, M. P. et al. Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis. Microbiology 150, 2669–2676 (2004).

  33. 33

    Suparak, S. et al. Multinucleated giant cell formation and apoptosis in infected host cells is mediated by Burkholderia pseudomallei type III secretion protein BipB. J. Bacteriol. 187, 6556–6560 (2005).

  34. 34

    Winstanley, C., Hales, B. A. & Hart, C. A. Evidence for the presence in Burkholderia pseudomallei of a type III secretion system-associated gene cluster. J. Med. Microbiol. 48, 649–656 (1999).

  35. 35

    Thibault, F. M., Valade, E. & Vidal, D. R. Identification and discrimination of Burkholderia pseudomallei, B. mallei, and B. thailandensis by real-time PCR targeting type III secretion system genes. J. Clin. Microbiol. 42, 5871–5874 (2004).

  36. 36

    Steinmetz, I., Rohde, M. & Brenneke, B. Purification and characterization of an exopolysaccharide of Burkholderia (Pseudomonas) pseudomallei. Infect. Immun. 63, 3959–3965 (1995).

  37. 37

    Atkins, T. et al. Characterisation of an acapsular mutant of Burkholderia pseudomallei identified by signature tagged mutagenesis. J. Med. Microbiol. 51, 539–547 (2002).

  38. 38

    Reckseidler-Zenteno, S. L., DeVinney, R. & Woods, D. E. The capsular polysaccharide of Burkholderia pseudomallei contributes to survival in serum by reducing complement factor C3b deposition. Infect. Immun. 73, 1106–1115 (2005).

  39. 39

    Matsuura, M., Kawahara, K., Ezaki, T. & Nakano, M. Biological activities of lipopolysaccharide of Burkholderia (Pseudomonas) pseudomallei. FEMS Microbiol. Lett. 137, 79–83 (1996).

  40. 40

    Utaisincharoen, P. et al. Kinetic studies of the production of nitric oxide (NO) and tumour necrosis factor-α (TNF-α) in macrophages stimulated with Burkholderia pseudomallei endotoxin. Clin. Exp. Immunol. 122, 324–329 (2000).

  41. 41

    Beutler, B. & Rietschel, E. T. Innate immune sensing and its roots: the story of endotoxin. Nature Rev. Immunol. 3, 169–176 (2003).

  42. 42

    Anuntagool, N. et al. Antigenic heterogeneity of lipopolysaccharide among Burkholderia pseudomallei clinical isolates. Southeast Asian J. Trop. Med. Public Health 31 (Suppl. 1), 146–152 (2000).

  43. 43

    Charuchaimontri, C. et al. Antilipopolysaccharide II: an antibody protective against fatal melioidosis. Clin. Infect. Dis. 29, 813–818 (1999).

  44. 44

    Anuntagool, N., Intachote, P., Wuthiekanun, V., White, N. J. & Sirisinha, S. Lipopolysaccharide from nonvirulent Ara+ Burkholderia pseudomallei isolates is immunologically indistinguishable from lipopolysaccharide from virulent Ara– clinical isolates. Clin. Diagn. Lab. Immunol. 5, 225–229 (1998).

  45. 45

    Anuntagool, N., Panichakul, T., Aramsri, P. & Sirisinha, S. Shedding of lipopolysaccharide and 200-kDa surface antigen during the in vitro growth of virulent Ara− and avirulent Ara+ Burkholderia pseudomallei. Acta Trop. 74, 221–228 (2000).

  46. 46

    Chua, K. L., Chan, Y. Y. & Gan, Y. H. Flagella are virulence determinants of Burkholderia pseudomallei. Infect. Immun. 71, 1622–1629 (2003).

  47. 47

    DeShazer, D., Brett, P. J., Carlyon, R. & Woods, D. E. Mutagenesis of Burkholderia pseudomallei with Tn5-OT182: isolation of motility mutants and molecular characterization of the flagellin structural gene. J. Bacteriol. 179, 2116–2125 (1997).

  48. 48

    Essex-Lopresti, A. E. et al. A type IV pilin, PilA, contributes to adherence of Burkholderia pseudomallei and virulence in vivo. Infect. Immun. 73, 1260–1264 (2005).

  49. 49

    Yang, H., Kooi, C. D. & Sokol, P. A. Ability of Pseudomonas pseudomallei malleobactin to acquire transferrin-bound, lactoferrin-bound, and cell-derived iron. Infect. Immun. 61, 656–662 (1993).

  50. 50

    Ashdown, L. R. & Koehler, J. M. Production of hemolysin and other extracellular enzymes by clinical isolates of Pseudomonas pseudomallei. J. Clin. Microbiol. 28, 2331–2334 (1990).

  51. 51

    Moore, R. A. et al. Contribution of gene loss to the pathogenic evolution of Burkholderia pseudomallei and Burkholderia mallei. Infect. Immun. 72, 4172–4187 (2004). Suggests that gene loss during the evolution of B. pseudomallei might have contributed to virulence.

  52. 52

    Takeda, K., Kaisho, T. & Akira, S. Toll-like receptors. Annu. Rev. Immunol. 21, 335–376 (2003).

  53. 53

    Santanirand, P., Harley, V. S., Dance, D. A., Drasar, B. S. & Bancroft, G. J. Obligatory role of γ interferon for host survival in a murine model of infection with Burkholderia pseudomallei. Infect. Immun. 67, 3593–3600 (1999). Highlights the essential role of IFN-γ in adequate host defence in melioidosis.

  54. 54

    Haque, A. et al. Role of T cells in innate and adaptive immunity against murine Burkholderia pseudomallei infection. J. Infect. Dis. 193, 370–379 (2006).

  55. 55

    Ekchariyawat, P. et al. Burkholderia pseudomallei-induced expression of suppressor of cytokine signaling 3 and cytokine-inducible Src homology 2-containing protein in mouse macrophages: a possible mechanism for suppression of the response to γ interferon stimulation. Infect. Immun. 73, 7332–7339 (2005).

  56. 56

    Hoppe, I. et al. Characterization of a murine model of melioidosis: comparison of different strains of mice. Infect. Immun. 67, 2891–2900 (1999).

  57. 57

    Leakey, A. K., Ulett, G. C. & Hirst, R. G. BALB/c and C57Bl/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis. Microb. Pathog. 24, 269–275 (1998).

  58. 58

    Lauw, F. N. et al. Elevated plasma concentrations of interferon (IFN)-γ and the IFN-γ-inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis. J. Infect. Dis. 180, 1878–1885 (1999).

  59. 59

    Brown, A. E. et al. Immune cell activation in melioidosis: increased serum levels of interferon-γ and soluble interleukin-2 receptors without change in soluble CD8 protein. J. Infect. Dis. 163, 1145–1148 (1991).

  60. 60

    Nuntayanuwat, S., Dharakul, T., Chaowagul, W. & Songsivilai, S. Polymorphism in the promoter region of tumor necrosis factor-α gene is associated with severe meliodosis. Hum. Immunol. 60, 979–983 (1999).

  61. 61

    Lauw, F. N. et al. The CXC chemokines γ interferon (IFN-γ)-inducible protein 10 and monokine induced by IFN-γ are released during severe melioidosis. Infect. Immun. 68, 3888–3893 (2000).

  62. 62

    Simpson, A. J. et al. Prognostic value of cytokine concentrations (tumor necrosis factor-α, interleukin-6, and interleukin-10) and clinical parameters in severe melioidosis. J. Infect. Dis. 181, 621–625 (2000).

  63. 63

    Lauw, F. N. et al. Soluble granzymes are released during human endotoxemia and in patients with severe infection due to Gram-negative bacteria. J. Infect. Dis. 182, 206–213 (2000).

  64. 64

    Lertmemongkolchai, G., Cai, G., Hunter, C. A. & Bancroft, G. J. Bystander activation of CD8+ T cells contributes to the rapid production of IFN-γ in response to bacterial pathogens. J. Immunol. 166, 1097–1105 (2001).

  65. 65

    Egan, A. M. & Gordon, D. L. Burkholderia pseudomallei activates complement and is ingested but not killed by polymorphonuclear leukocytes. Infect. Immun. 64, 4952–4959 (1996).

  66. 66

    Frank, M. M., Joiner, K. & Hammer, C. The function of antibody and complement in the lysis of bacteria. Rev. Infect. Dis. 9 (Suppl. 5), S537–S545 (1987).

  67. 67

    Dharakul, T. et al. HLA-DR and-DQ associations with melioidosis. Hum. Immunol. 59, 580–586 (1998).

  68. 68

    Ketheesan, N. et al. Demonstration of a cell-mediated immune response in melioidosis. J. Infect. Dis. 186, 286–289 (2002).

  69. 69

    Barnes, J. L. et al. Adaptive immunity in melioidosis: a possible role for T cells in determining outcome of infection with Burkholderia pseudomallei. Clin. Immunol. 113, 22–28 (2004).

  70. 70

    Utaisincharoen, P. et al. Induction of iNOS expression and antimicrobial activity by interferon (IFN)-β is distinct from IFN-γ in Burkholderia pseudomallei-infected mouse macrophages. Clin. Exp. Immunol. 136, 277–283 (2004).

  71. 71

    Chierakul, W. et al. Disease severity and outcome of melioidosis in HIV coinfected individuals. Am. J. Trop. Med. Hyg. 73, 1165–1166 (2005).

  72. 72

    Jones, A. L., Beveridge, T. J. & Woods, D. E. Intracellular survival of Burkholderia pseudomallei. Infect. Immun. 64, 782–790 (1996).

  73. 73

    Pruksachartvuthi S, A. N. & Thankerngpol, K. Survival of Pseudomonas pseudomallei in human phagocytes. J. Med. Microbiol. 31, 109–114 (1990).

  74. 74

    Egan, A. M. & Gordon, D. L. Burkholderia pseudomallei activates complement and is ingested but not killed by polymorphonuclear leukocytes. Infect. Immun. 64, 4952–4959 (1996).

  75. 75

    Kespichayawattana, W., Rattanachetkul, S., Wanun, T., Utaisincharoen, P. & Sirisinha, S. Burkholderia pseudomallei induces cell fusion and actin-associated membrane protrusion: a possible mechanism for cell-to-cell spreading. Infect. Immun. 68, 5377–5384 (2000).

  76. 76

    Mohamed, R., Nathan, S., Embi, N., Razak, N. & Ismail, G. Inhibition of macromolecular synthesis in cultured macrophages by Pseudomonas pseudomallei exotoxin. Microbiol. Immunol. 33, 811–820 (1989).

  77. 77

    Dejsirilert, S., Kondo, E., Chiewsilp, D. & Kanai, K. Growth and survival of Pseudomonas pseudomallei in acidic environments. Jpn J. Med. Sci. Biol. 44, 63–74 (1991).

  78. 78

    Utaisincharoen, P., Tangthawornchaikul, N., Kespichayawattana, W., Chaisuriya, P. & Sirisinha, S. Burkholderia pseudomallei interferes with inducible nitric oxide synthase (iNOS) production: a possible mechanism of evading macrophage killing. Microbiol. Immunol. 45, 307–313 (2001).

  79. 79

    Harley, V. S., Dance, D. A., Drasar, B. S. & Tovey, G. Effects of Burkholderia pseudomallei and other Burkholderia species on eukaryotic cells in tissue culture. Microbios 96, 71–93 (1998).

  80. 80

    Harley, V. S., Dance, D. A., Tovey, G., McCrossan, M. V. & Drasar, B. S. An ultrastructural study of the phagocytosis of Burkholderia pseudomallei. Microbios 94, 35–45 (1998).

  81. 81

    Breitbach, K. et al. Actin-based motility of Burkholderia pseudomallei involves the Arp 2/3 complex, but not N-WASP and Ena/VASP proteins. Cell. Microbiol. 5, 385–393 (2003). Excellent study that added to our understanding of the intracellular lifestyle of B. pseudomallei.

  82. 82

    Stevens, M. P. et al. Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei. Mol. Microbiol. 56, 40–53 (2005). Further dissects the role of protein–protein interaction leading to the initiation of actin polymerization by B. pseudomallei.

  83. 83

    Wong, K. T., Puthucheary, S. D. & Vadivelu, J. The histopathology of human melioidosis. Histopathology 26, 51–55 (1995).

  84. 84

    Sun, G. W., Lu, J., Pervaiz, S., Cao, W. P. & Gan, Y. H. Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cell. Microbiol. 7, 1447–1458 (2005).

  85. 85

    Inglis, T. J. et al. Interaction between Burkholderia pseudomallei and Acanthamoeba species results in coiling phagocytosis, endamebic bacterial survival, and escape. Infect. Immun. 68, 1681–1686 (2000).

  86. 86

    Stevens, M. P. & Galyov, E. E. Exploitation of host cells by Burkholderia pseudomallei. Int. J. Med. Microbiol. 293, 549–555 (2004).

  87. 87

    Brown, N. F., Boddey, J. A., Flegg, C. P. & Beacham, I. R. Adherence of Burkholderia pseudomallei cells to cultured human epithelial cell lines is regulated by growth temperature. Infect. Immun. 70, 974–980 (2002).

  88. 88

    Kespichayawattana, W., Intachote, P., Utaisincharoen, P. & Sirisinha, S. Virulent Burkholderia pseudomallei is more efficient than avirulent Burkholderia thailandensis in invasion of and adherence to cultured human epithelial cells. Microb. Pathog. 36, 287–292 (2004).

  89. 89

    Cheng, A. C., Stephens, D. P., Anstey, N. M. & Currie, B. J. Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis. Clin. Infect. Dis. 38, 32–37 (2004). A retrospective study showing a fall in mortality of septic melioidosis with adjunctive G-CSF treatment.

  90. 90

    Powell, K., Ulett, G., Hirst, R. & Norton, R. G-CSF immunotherapy for treatment of acute disseminated murine melioidosis. FEMS Microbiol. Lett. 224, 315–318 (2003).

  91. 91

    Cheng, A. C. Meliodosis: Epidemiology, Pathophysiology And Management. Ph.D. thesis, Flinders University of South Australia (2005).

  92. 92

    Utaisincharoen, P. et al. CpG ODN enhances uptake of bacteria by mouse macrophages. Clin. Exp. Immunol. 132, 70–75 (2003).

  93. 93

    Wongratanacheewin, S. et al. Immunostimulatory CpG oligodeoxynucleotide confers protection in a murine model of infection with Burkholderia pseudomallei. Infect. Immun. 72, 4494–4502 (2004). Evaluation of a potential new immunomodulatory treatment target in melioidosis.

  94. 94

    Warawa, J. & Woods, D. E. Melioidosis vaccines. Expert Rev. Vaccines 1, 477–482 (2002).

  95. 95

    Atkins, T. et al. A mutant of Burkholderia pseudomallei, auxotrophic in the branched chain amino acid biosynthetic pathway, is attenuated and protective in a murine model of melioidosis. Infect. Immun. 70, 5290–5294 (2002).

  96. 96

    Brett, P. J., Mah, D. C. & Woods, D. E. Isolation and characterization of Pseudomonas pseudomallei flagellin proteins. Infect. Immun. 62, 1914–1919 (1994).

  97. 97

    Nelson, M. et al. Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis. J. Med. Microbiol. 53, 1177–1182 (2004).

  98. 98

    Iliukhin, V. I. et al. Burkholderia thailandensis: biological properties, identification and taxonomy. Mol. Gen. Mikrobiol. Virusol. 7–11 (2002).

  99. 99

    Healey, G. D., Elvin, S. J., Morton, M. & Williamson, E. D. Humoral and cell-mediated adaptive immune responses are required for protection against Burkholderia pseudomallei challenge and bacterial clearance postinfection. Infect. Immun. 73, 5945–5951 (2005).

  100. 100

    Ou, K. et al. Integrative genomic, transcriptional, and proteomic diversity in natural isolates of the human pathogen Burkholderia pseudomallei. J. Bacteriol. 187, 4276–4285 (2005).

  101. 101

    Mahenthiralingam, E., Urban, T. A. & Goldberg, J. B. The multifarious, multireplicon Burkholderia cepacia complex. Nature Rev. Microbiol. 3, 144–156 (2005).

  102. 102

    Payne, G. W. et al. Development of a recA gene-based identification approach for the entire Burkholderia genus. Appl. Environ. Microbiol. 71, 3917–3927 (2005).

Download references


We thank members of the Wellcome Trust–Oxford University–Mahidol University Tropical Medicine Research Programme for their support, in particular V. Wuthiekanun and W. Chierakul. We thank the staff of Sappasithiprasong Hospital for many years of fruitful collaboration; special thanks go to W. Chaowagul. W.J.W. is supported by the Dutch Foundation for Tropical Research (WOTRO). S.J.P. is supported by a Wellcome Trust Career Development Award in Clinical Tropical Medicine.

Author information

Correspondence to W. Joost Wiersinga.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links


Entrez Genome Project

Burkholderia mallei

Burkholderia pseudomallei

Burkholderia thailandensis

Escherichia coli

Ralstonia solanacearum

Salmonella enterica serovar Typhimurium

Shigella flexneri


Wellcome Trust South-East Asia Programme in Thailand

B. pseudomallei genome sequence

The Institute for Genomic Research (TIGR)

CDC list of bioterrorism agents

BICHAT, the European Commission's Task Force on biological and chemical threats


Genomic islands

Clusters of genes that have been imported from unrelated bacterial taxa through horizontal gene transfer, and which might help the bacterium to acquire a new (possibly pathogenic) lifestyle.

Shotgun sequencing

A genomic sequencing strategy that involves random fragmentation of large DNA segments. The fragments are sequenced, and programs with highly refined algorithms are used to reassemble the original DNA sequence.

Multilocus sequence typing

(MLST). A method for the genotypic characterization of prokaryotes at the infraspecific level, using the allelic mismatches of a small number of housekeeping genes. Designed as a tool in molecular epidemiology and used for recognizing distinct strains within named species.

Subtractive hybridization

A technique used to identify differentially expressed genes. The DNA species present in one sample are specifically enriched by hybridization with nucleic acids from another sample and by removing the associated double-stranded molecules.

Quorum sensing

A system by which bacteria communicate. Signalling molecules — chemicals similar to pheromones that are produced by an individual bacterium — can affect the behaviour of surrounding bacteria.


A part of the innate immune system comprising serum proteins that can protect against infection.

Limulus amoebocytelysate assay

A chromogenic assay used to monitor endotoxin production.

Natural killer (NK) cells

Lymphocytes that do not express the T-cell receptor or B-cell receptor and that mediate natural killing against prototypical NK-cell-sensitive targets.

Human leukocyte antigen

(HLA). Also known as major histocompatibility complex (MHC), a glycoprotein that is found on the surface of antigen-presenting cells that presents antigen for recognition by TH cells.

Rights and permissions

Reprints and Permissions

About this article

Further reading